A Dissertation on
ASSESSMENT OF PULMONARY FUNCTION IN TYPE 2 DIABETES MELLITUS AND ITS CORRELATION WITH GLYCEMIC STATUS
Dissertation Submitted to
THE TAMILNADU Dr.M.G.R. MEDICAL UNIVERSITY CHENNAI - 600 032
With partial fulfillment of the regulations for the award of the degree of
M.D. GENERAL MEDICINE BRANCH-I
COIMBATORE MEDICAL COLLEGE, COIMBATORE MAY 2020
REGISTRATION NUMBER - 201711310
CERTIFICATE - I
This is to certify that this dissertation titled “ASSESSMENT OF PULMONARY FUNCTION IN TYPE 2 DIABETES MELLITUS AND ITS CORRELATION WITH GLYCEMIC STATUS” has been done by DR.MAHA RANI ALIAS MAHA SWETHA J under my guidance.
Further certified that this work is an original, embodying study of bonafide cases.
Professor and Head of the Department, Department of Medicine,
Coimbatore Medical College Hospital, Coimbatore.
Department of Medicine,
Coimbatore Medical College Hospital, Coimbatore.
Dean,
Coimbatore Medical College Hospital, Coimbatore.
CERTIFICATE – II
This is to certify that this dissertation work titled “ASSESSMENT OF PULMONARY FUNCTION IN TYPE 2 DIABETES MELLITUS AND ITS CORRELATION WITH GLYCEMIC STATUS”of the candidate Dr.MAHA RANI ALIAS MAHA SWETHA J with Registration Number 201711310 for the award of DOCTOR OF MEDICINE in the branch of GENERAL MEDICINE. I have personally verified with the urkund.com website for plagiarism Check. I found that the uploaded thesis file from the introduction to conclusion page had 10% plagiarism.
GUIDE & SUPERVISOR SIGN WITH SEAL.
DECLARATION
I solemnly declare that the dissertation titled “ASSESSMENT OF PULMONARY FUNCTION IN TYPE 2 DIABETES MELLITUS AND ITS CORRELATION WITH GLYCEMIC STATUS” was done by me under the guidance and supervision of Prof.Dr.K.SWAMINATHAN, M.D. This dissertation is submitted to The Tamilnadu Dr. M.G.R. Medical University towards the partial fulfillment of the requirement for the award of MD Degree in General Medicine (Branch I)
DR.MAHA RANI ALIAS MAHA SWETHA J
Date:
Place:
ACKNOWLEDGEMENT
I wish to express my sincere thanks to our respected Dean Dr.B.ASOKAN MS MCH , for having allowed me to conduct this study in our hospital.
I express my heartfelt thanks and deep gratitude to the Head of the Department of Medicine Prof. Dr. K.SWAMINATHAN, M.D. for his generous help and guidance in the course of the study.
I am extremely grateful to Dr.KEERTHIVASAN MD, HOD Dept of thoracic medicine , for his valuable help and cooperation and allowing me to use institutional facilities.
I am extremely grateful to Dr.MANIMEGALAI, M.D, HOD, Department of Biochemistry, for the valuable help and cooperation and allowing me to use institutional facilities.
I sincerely thank my Assistant Professors- Dr.ALAGU THIYAGARAJAN MD, Dr.V.MANOJ KUMAR MD, for their guidance and kind help.
I express my sincere thanks to all my friends and post-graduate colleagues for their whole hearted support and companionship during my studies.
I thank all my PATIENTS, who formed the backbone of this study without whom this study would not have been possible.
I am ever grateful to the ALMIGHTY GOD for always showering their blessings on me and my family.
Dr.MAHA RANI ALIAS MAHA SWETHA J
INDEX
S.NO. CONTENT PAGE NO.
1. Introduction 1
2. Aims and objectives 3
3. Review of literature 4
4. Material and Methods 40
5. Results 43
6. Discussion and conclusion 77
7. Limitations of the study 78
8. Bibliography
9.
Annexure Proforma Consent form Master chart
LIST OF TABLES
S.NO TITLE PAGE NO.
1.
DIFFERENCE BETWEEN OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASE
37
2. AGE DISTRIBUTION 43
3. SEX DISTRIBUTION 44
4. DISTRIBUTION OF DURATION OF DISEASE 45
5. DISTRIBUTION OF TYPE OF TREATMENT 46
6. DISTRIBUTION OF FASTING BLOOD SUGAR 47
7. DISTRIBUTION OF HbA1C 48
8. DISTRIBUTION OF BODY MASS INDEX 49
9. DISTRIBUTION OF FVC % PREDICTED 50
10. DISTRIBUTION OF FEV1/FVC % PREDICTED 51
11.
DISTRIBUTION OF PATTERN OF IMPAIRMENT OF LUNG FUNCTION
52
12. CORRELATION OF FVC % PREDICTED WITH FBS 53 13. CORRELATION OF FEV1 % PREDICTED WITH FBS 55
14.
CORRELATION OF FEV1/FVC % PREDICTED WITH FBS
57
15.
CORRELATION OF FVC % PREDICTED WITH HbA1C
59
16.
CORRELATION OF FEV1 % PREDICTED WITH HbA1C
61
17. CORRELATION OF FEV1/FVC % PREDICTED WITH HbA1C
63
18. CORRELATION OF FVC % PREDICTED WITH DURATION OF DISEASE
65
19. CORRELATION OF FEV1 % PREDICTED WITH DURATION OF DISEASE
67
20. CORRELLATION OF FEV1/FVC (% PREDICTED) WITH DURATION OF DISEASE
69
21. CORRELATION DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH DURATION OF DISEASE
71
22. CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH HBA1C
73
23. CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH FBS
75
LIST OF FIGURES
S.NO. TITLE PAGE NO.
1.
PROINSULIN- A & B CHAIN OF MATURE INSULIN ALONG WITH C PEPTIDE
7
2. MECHANISM OF SECRETION OF INSULIN. 8
3.
METABOLIC PATHWAY SHOWING FUEL METABOLISM & INSULIN ACTIONS
10
4. DIABETIC DERMOPATHY 17
5. DIABETIC NECROBIOSIS LIPOIDICA DIABETICORUM 18
6. DIABETIC ERUPTIVE XANTHOMATOSIS 19
7. CLINICAL TYPES OF DIABETIC NEUROPATHY 23
8. DIABETIC RETINOPATHY 28
9. ALVEOLAR STRUCTURE 30
10. LUNG VOLUME GRAPH 33
11. NORMAL SPIROMETRY GRAPH 34
12. FLOW-VOLUME LOOP - OBSTRUCTIVE PATTERN 35
13. FLOW-VOLUME LOOP - RESTRICTIVE PATTERN 36
LIST OF CHARTS
S.NO TITLE PAGE NO.
1. AGE DISTRIBUTION 43
2. SEX DISTRIBUTION 44
3. DISTRIBUTION OF DURATION OF DISEASE 45
4. DISTRIBUTION OF TYPE OF TREATMENT 46
5. DISTRIBUTION OF FASTING BLOOD SUGAR 47
6. DISTRIBUTION OF HbA1C 48
7. DISTRIBUTION OF BODY MASS INDEX 49
8. DISTRIBUTION OF FVC % PREDICTED 50
9. DISTRIBUTION OF FEV1/FVC % PREDICTED 51
10.
DISTRIBUTION OF PATTERN OF IMPAIRMENT OF LUNG FUNCTION
52
11. CORRELATION OF FVC % PREDICTED WITH FBS 54
12. CORRELATION OF FEV1 % PREDICTED WITH FBS 56
13.
CORRELATION OF FEV1/FVC % PREDICTED WITH FBS
58
14.
CORRELATION OF FVC % PREDICTED WITH HbA1C
60
15.
CORRELATION OF FEV1 % PREDICTED WITH HbA1C
62
16. CORRELATION OF FEV1/FVC % PREDICTED WITH HbA1C
64
17. CORRELATION OF FVC % PREDICTED WITH DURATION OF DISEASE
66
18. CORRELATION OF FEV1 % PREDICTED WITH DURATION OF DISEASE
68
19. CORRELLATION OF FEV1/FVC (% PREDICTED) WITH DURATION OF DISEASE
70
20. CORRELATION DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH DURATION OF DISEASE
72
21. CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH HBA1C
74
22. CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH FBS
76
LIST OF ABBREVATIONS
WHO - World Health Organization
DM - Diabetes Mellitus
MODY – Maturity Onset Diabetes Of Young FPG – Fasting Plasma Glucose
FBS – Fasting Blood Sugar
OGTT – Oral Glucose Tolerance Test IGF – Insulin Like Growth Factor GIT – Gastrointestinal Tract GLP – Glucagon Like Peptide
FFA – Free Fatty Acid
PCOS – Polycystic Ovarian Syndrome GDM – Gestational Diabetes Mellitus TGF – Transforming Growth Factor GFR – Glomerular Filtration Rate
ICAM – Intra Cellular Adhesion Molecule CHD – Coronary Heart Disease
PFT – Pulmonary Function Test TLC – Total Lung Capacity FVC – Forced Vital Capacity
FEV1 – Forced Expiratory Volume 1st Second MMEF – Maximum Mid Expiratory Flow
FEF – Forced Expiratory Flow
PEF – Peak Expiratory Flow
IDDM – Insulin Dependent Diabetes Mellitus NIDDM – Non Insulin Dependent Diabetes Mellitus
1
INTRODUCTION
The number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014 1.The global prevalence of diabetes among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014 1.Diabetes prevalence has been rising more rapidly in middle- and low-income countries.
There is an alarming increase in the incidence and prevalence of diabetes mellitus (DM) in Asian Indians 2.Type 2 Diabetes mellitus is a result impaired insulin secretion, reduced tissue sensitivity to insulin or coexistence of both.
Diabetes is characterized by persistent hyperglycemia and abnormal metabolisms of carbohydrates, proteins and lipids. Diabetes mellitus is associated with long term damage and dysfunction and also failure of various organs and its complications are mostly caused by macro vascular and micro vascular damages3, 4. Though there is great importance given to the diabetic complications in the cardiovascular renal, ocular and neurological the pulmonary complications of type 2 diabetes mellitus have been poorly characterized. The alveolar capillary network in the lung is a large micro- vascular unit and has a major risk of being affected by microangiopathy. But because of its large reserve, substantial loss of the microvascular bed is tolerated without developing dyspnoea. As a result, pulmonary diabetic micro- angiopathy is under-recognized clinically. Reduced elastic recoil, reduced lung volume, diminished respiratory muscle performance, chronic low grade inflammation,5,6 decrease in pulmonary diffusion capacity for carbon
2
monoxide7 autonomic neuropathy involving respiratory muscles8 are some of the important changes occurring in DM.
JUSTIFICATION FOR THE STUDY
The pulmonary complications of type 2 diabetes mellitus have been poorly studied.
These complications have a significant impact on the quality of life of the affected individuals and they impose a heavy burden on health care providers worldwide.
Relatively few studies have been done on pulmonary mechanical function. The present study focuses on this aspect and its correlation with glycemic control and duration of disease.
3
AIMS AND OBJECTIVES
The study aims to evaluate the pulmonary function in type 2 DM patients
To determine the correlation of pulmonary function with the glycemic control and duration of the disease.
4
REVIEW OF LITERATURE
INTRODUCTION:
Diabetes mellitus is a heterogeneous group of metabolic disorders which is characterized by chronic hyperglycemia. It is considered as a leading cause of increasing morbidity and deaths in today’s world. Complex interaction of various factors including environmental & genetic is the cause for several distinct types diabetes mellitus.
The factors contributing to hyperglycemia are decrease in insulin secretion, decrease in utilization of glucose, and increase in glucose production. This dysregulation causes secondary changes in various organ systems and imposing burden on the person with diabetes and also on the health care system.9
According to the latest 2016 data from the World Health Organization (WHO) there is an estimated 422 million adults who are living with diabetes.10 As per the data from the International Diabetes Federation in 2013 put there were 381 million people having diabetes.11 This is expected to almost double by 203012 of this Type 2 DM makes up about 85-90% of all cases.13,14
The greatest increase of the prevalence is occurring in low- and middle- income countries10 including in Asia and Africa, this is because of the urbanization and lifestyle changes. It was estimated by The WHO that diabetes
5
has resulted in 1.5 million deaths in 2012 and it was the 8th leading cause of death.10
Etiological Classification of Diabetes Mellitus15,16,17
6
DIAGNOSTIC CRITERIA FOR DIABETES ADA GUIDELINES15,16,17
7
INSULIN : BIOSYNTHESIS, SECRETION AND ACTION
Insulin is produced by the beta cells of the islets of pancreas. It is synthesized as preproinsulin which is a precursor polypeptide having single chain 86- amino acid. After production it undergoes proteolysis to give rise to proinsulin, which is related to IGF 1 & 2 structurally. Further cleavage of the proinsulin forms A & B chains of insulin and the C peptide. The beta cells store them together & in secretory granules which are then co secreted9.
Figure 1. Showing PROINSULIN (A & B chain of mature insulin along with C peptide )
8
SECRETION:
Insulin is secreted by beta cells of pancreas. The secretion is influenced by many factors such as amino acids, nutrients, ketones, and GI peptides, the important regulator is glucose. There occurs enhancement of protein translation and its processing for Insulin synthesis when glucose levels are above 70mg/dl.
Glucokinase mediated glucose phosphorylation is the rate limiting step that controls the insulin secretion related to glucose regulation. Depolarization of beta cell membrane induced by potassium channel inhibition7.will cause opening up of calcium channels and then there is insulin secretion.
Figure 2. Showing mechanism of secretion of insulin.
9
GLUT-2 mediates intracellular transport of glucose , it will undergoes oxidation to produce ATP which will inhibit potassium channel receptor on Beta cell leading in to depolarization and Ca2 ion influx followed by release of stored insulin.
GIT also plays a role by releasing incretins from the neuroendocrine cells after ingestion of food and thereby amplifies insulin secretion and suppresses secretion of glucagon. The L- cells of the small intestine will release GLP-1 which stimulates secretion of insulin usually when blood glucose is more than the fasting level.
10
Figure 3. Metabolic pathway showing fuel metabolism & insulin actions 18:
( + ) ---> Stimulation by insulin ( - ) ---> inhibition by insulin FFA ---> Free fatty acids
11
PATHOGENESIS OF T2 DM
The sequence of events in most of the patients with type 2 diabetes is insulin resistance, progressive beta-cell failure, and glucose toxicity. All Patients with insulin resistance syndrome may not progress to type 2 diabetes .Insulin resistance is a pathophysiologic condition wherein a normal amount of insulin fails to maintain glucose homeostasis 19. Insulin resistance by itself is not a disease. Insulin resistance and another defect together leads to disease state20,21 . Thus the occurrence of disease is a "two hit" phenomenon, with insulin resistance being the first hit. Insulin resistance is defined as a pathophysiologic condition wherein a normal amount of insulin fails to lead to normal glucose regulation. The two main examples of insulin resistance leading to disease are the polycystic ovarian syndrome (PCOS) and type 2 diabetes mellitus. In both these conditions, the first "hit" is an underlying insulin resistance, but ultimately a second "hit" is needed to cause the disease. In diabetes, the beta cells have a progressive decrease in insulin secretory function either because of genetic abnormalities or long-standing excessive secretory stress or glucose toxicity. As a result of insulin secretion decreases the muscle becomes insulin deficient and postprandial hyperglycemia occurs. It is the first disturbance in type 2 diabetes and precedes fasting hyperglycemia by approximately 5 years .As insulin secretion decreases further, glucose homeostasis in liver is deranged and fasting hyperglycemia occurs. There are also other conditions in which insulin resistance plays an important role as in hypertension, dyslipidemia, and atherosclerosis, which also comprise the insulin resistance syndrome. The common causes of insulin resistance include sedentary life style, obesity , increased counter regulatory hormones .
12
Visceral obesity: Visceral (central) obesity is strongly associated with insulin resistance. Visceral adiposity is characterized by abdominal/truncal obesity of the
"spare tire" in the belly. The unique nature of the visceral fat is that it directly into the liver via the portal circulation and is metabolically more active than subcutaneous adipose tissue leading to direct drainage of free fatty acids, and perhaps other substances into the liver. This is hypothesized to be one of the causes of insulin resistance. Abdominal waist circumference can be used as a surrogate marker of visceral obesity. It varies with gender, racial, and ethnic differences. Weight loss improves insulin sensitivity in obese individuals. Modest decrease of weight in obese type 2 diabetic persons shows a significant improvement in glycemic control22.
DEFECTIVE 1ST PHASE INSULIN SECRETION:
Insulin secretion is biphasic in normal beta cells .The 1st phase of insulin secretion helps in priming the insulin target tissues to maintain the normal glucose homeostasis. It is one of the early manifestations, which is found to occur when fasting glucose rise to 115-120mg%
DEFECTIVE PULSATILE INSULIN SECRETION:
Insulin is normally secreted in pulses of rapid frequency.23 Abnormal oscillatory insulin secretion is the characteristic of earlier part of type 2 diabetes.
Decrease in insulin secretion:
Following a defective insulin secretion and glucotoxicity and progressive loss of beta cell function there is a stage of decrease in insulin secretion representing a beta
13
cell failure. The United Kingdom Prospective Diabetes Study (UKPDS) gives us data concerning decreasing beta-cell function 24,25.The data from the study showed that type 2 diabetes is associated with a progressive decrease in beta-cell function that continues throughout the course of the disease, and is unaltered by dietary, sulfonylurea, or metformin therapy.
RISK FACTORS FOR TYPE 2 DIABETES MELLITUS:
1) History of diabetes mellitus in family members 2) Obese ( Body mass index > 25/meter square) 3) Sedentary life
4) Past history of Impaired fasting glucose or Impaired glucose tolerance or and A1c of 5.7 – 6.4%
5) Past History of gestational diabetes mellitus or delivery of a baby of > 4 kilograms
6) High density cholesterol < 35 milligrams/dl (0.90 mmol/L) and /or a triglyceride > 250milligrams/dl (2.82mmol/L)
7) Polycystic ovarian disease 8) History of vascular disease 9) History of cardiac disease
10) Hypertension of more than 140/90
14
SCREENING FOR T2DM 26
Criteria:
* Overweight and obese children
o BMI >85th percentile for age and sex
o Weight for height >85th percentile
o >120% of ideal weight for height Plus any two of the following risk factors:
Family history of T2DM in first or second-degree relative
Race/Ethnicity – African , Asian
Signs of insulin resistance or conditions associated with insulin resistance
Acanthosis nigricans
PCOS
Hypertension
Dyslipidemia
Small for gestational age birth weight
Maternal history of diabetes or GDM during the child's gestation
Age of initiation: age 10 years or at onset of puberty, if puberty occurs at a younger age
15
CLINICAL FEATURES
Frequent urination
Excessive thirst
Unexplained weight loss
Extreme hunger
Sudden vision changes
Tingling or numbness in the hands or feet
Feeling very tired much of the time
Very dry skin
Sores that are slow to heal
More infections than usual
16
COMPLICATIONS OF T2 DM
SKIN27
BACTERIAL INFECTIONS
Many kinds of bacterial infections occur commonly in people with diabetes:
Styes (infections of the glands of the eyelid)
Boils
Folliculitis
Carbuncles
Infections around the nails
FUNGAL INFECTIONS
Most common fungal infection of people with diabetes is Candida albicans. It is a yeast-like fungus. Symptoms commonly include itchy rashes of moist, red areas that are surrounded by tiny blisters and scaling. Common sites include areas are under the breasts, around the nails, intertrigal areas, in the corners of the mouth, under the penile foreskin and in the armpits and groin. Other Common fungal infections include athlete’s foot, ringworm and vaginal infection that causes itching and curdy white leucorrhea.
17
OTHER DIABETES-RELATED SKIN CONDITIONS
ACANTHOSIS NIGRICANS
Acanthosis nigricans is a condition that indicates the underlying insulin resistance in diabetic patients. It appears as tan or brown velvety raised areas on the sides and back of the neck, armpits and groin. Rarely it can also occur on the hands, elbows and knees.
DIABETIC DERMOPATHY
Diabetes causes changes in the small blood vessels (microvasculature). This leads on to changes in the skin called diabetic dermopathy. It appears like light brown, scaly patches which may be oval or circular. They are most often seen on the front of both legs. It does not lead on to further problems such as ulceration or itching.
FIGURE 4 – DIABETIC DERMOPATHY
18
NECROBIOSIS LIPOIDICA DIABETICORUM
Necrobiosis lipoidica diabeticorum (NLD) is rare skin condition that is caused due to the microvasculature changes that diabetes cause .it produces lesions similar to diabetic dermopathy, but they appear larger, and deeper, which starts as a dull, red, raised lesions. Later it looks like a shiny scar Sometimes it may become itchy and painful and ulcerate.
FIGURE 5 - NECROBIOSIS LIPOIDICA DIABETICORUM
ERUPTIVE XANTHOMATOSIS
Eruptive xanthomatosis is condition caused by uncontrolled diabetes. It appears firm, yellow, raised lesions in the skin that are itchy which occurs most commonly on the backs of hands, feet, arms, legs and buttocks.It is a indicator of high levels of cholesterol.
19
FIGURE 6 - ERUPTIVE XANTHOMATOSIS
METABOLIC COMPLICATIONS
The two main metabolic complication of diabetes include 1. Diabetic Ketoacidosis
2. Hyperglycaemic Hyperosmolar Nonketotic Coma
DIABETIC KETOACIDOSIS28
It occurs because of lack of insulin leading to mobilization of fatty acids from adipose tissue because of the lipase activity that breaks down triglycerides into fatty acids and glycerol. The increased fatty acid levels leads to ketone production by the liver
PRECIPITATING FACTORS:
Physical or emotional stress such as infection, pregnancy, or extreme anxiety, omission or inadequate use of insulin.
20
CLINICAL FEATURES:
The presentation varies with severity and co morbid conditions. Polyuria with polydipsia is the most common presenting symptom other common symptoms included weight loss, fatigue, dyspnoea, vomiting, preceding febrile illness, abdominal pain.
SIGNS:
Dehydration causes tachycardia, poor skin turgor, dry mucous membranes, and orthostatic hypotension. The metabolic acidosis may lead to compensatory deep (Kussmaul) respirations, fruity smell on the patient’s breath. Mental status can vary from somnolence to lethargy and coma.
LABORATORY INVESTIGATION :
Serum glucose level (greater than 250 mg per dL ), An elevated serum ketone level
PH less than 7.3
Serum bicarbonate, measurement of electrolytes, phosphate, blood urea and creatinine; urinalysis; complete blood count with differential; and ECG , Chest radiography and urine and blood cultures should be added for further evaluation of infection.
21
TREATMENT GOALS:
To improve circulatory volume and tissue perfusion.
To decrease serum glucose
To correct the acidosis and electrolyte imbalances.
These objectives usually are accomplished through the administration of insulin and intravenous fluid and electrolyte replacement solutions.
Identification and treatment of the underlying cause.
THE HYPERGLYCEMIC HYPEROSMOLAR NONKETOTIC (HHNK) SYNDROME
HHNK - blood glucose >600 mg/dL
Hyperosmolarity -plasma osmolarity >310 mOsm/L Dehydration and depression of the sensorium.
The absence of ketoacidosis,
CLINICAL FEATURES: dehydration, encephalopathy ,Excessive thirst .
TREATMENT GOALS:
Reduction of glucose level to 250 to 350 mg per dL .
In patients with hyperosmolar hyperglycemia, the mean fluid loss is approximately 9 L requiring adequate fluid correction.
22
Judicious medical observation because during treatment there is a threat of cerebral edema .
Electrolyte correction including potassium, sodium and phosphate.
DIABETIC NEUROPATHY
A recent study done in south India revealed 19.1% incidence rate of peripheral neuropathy in Type 2 DM28. it is one of the most commonest causes of peripheral neuropathy. Autonomic neuropathy due to diabetes causes death in 25%-50% within a period of 5-10 years29,30. In another study, an increase in incidence of neuropathy from 7.5% to 50% at 25 years follow up has been documented.
CLINICAL CLASSIFICATION OF DIABETIC NEUROPATHY:
SYMMETRIC :
1. Polyneuropathy
2. Painful autonomic neuropathy
3. Painful distal neuropathy with loss of weight known as “diabetic cachexia”
4. Insulin neuritis
5. Polyneuropathy after DKA 6. CIDP with diabetes mellitus
23
ASYMMETRIC :
1. Radiculoplexoneuropathies ( lumbosacral, thoracic, cervical ) 2. Mononeuropathies
3. Median neuropthy ( wrist ) 4. Ulnar neuropathy (elbow )
5. Peroneal neuropathy ( fibular head )
FIGURE 7 - CLINICAL TYPES OF DIABETIC NEUROPATHY
24
Various clinical features of diabetic autonomic neuropathy are : Resting tachycardia
Orthostatic hypotension
Bladder emptying abnormalities
Sympathetic nervous system dysfunction ( hyperhidrosis, anhidrosis )
Hypoglycaemic unawareness.
PATHOGENESIS OF DIABETIC NEUROPATHY:
Hyperglycemia causes increased endothelial vascular resistance and reduce the nerve blood flow. It will also decreases the level of myoinositol in nerve fibres. There is accumulation of fructose and sorbitol in nerve that leads to non-enzymatic glycosylation of nerve proteins. Protein kinase C activation plays a major role in vascular damage to nerve that results in defective axonal transport9.
DIAGNOSIS :
It includes assessment of muscle power.
Testing of posterior column and temperature sensations. (Tuning fork of 128 Hz is used for testing vibration sense) .
The tests based on blood pressure and heart rate response to specific manoeuvres are used to assess autonomic functions.
25
Nerve biopsy to exclude other causes of neuropathy. The American academy of neurology has recommended that DN should be diagnosed in the presence of sensory or autonomic neuropathy only after excluding other causes31. The nerve conduction velocity is diminished gradually in DN, with an estimated loss of about 0.5/sec/year32. DIABETIC NEPHROPATHY :
Diabetic nephropathy is the common cause of end-stage renal disease, accounting for 40% of new cases33 .The term diabetic nephropathy is used to describe the lesions that occur in the diabetic kidney. It is characterised by by increased urinary albumin excretion in the absence of other renal diseases. Hyperglycaemic stress mainly affects the glomeruli. The glomerular changes that occur including capillary basement membrane thickening diffuse glomerular sclerosis, and nodular glomerulosclerosis.
PATHOGENESIS: Hyperglycemia causes increased expression of transforming growth factor-beta (TGF-beta) in the glomeruli34. TGF-beta causes cellular hypertrophy and enhanced collagen synthesis. Patients with overt diabetic nephropathy (dipstick-positive proteinuria and decreasing GFR) in addition to the renal hemodynamic alterations, also develop systemic hypertension. Hypertension further adds to The deleterious effects of diabetes .
26
STAGES OF DIABETIC NEPHROPATHY
DIABETIC RETINOPATHY:
The ocular complication of diabetes include cataract, glaucoma, most importantly retinopathy. Diabetic retinopathy is characterized by abnormal retinal vascular permeability, macular edema, microaneurysm, neovascularization and associated hemorrhage, scarring, and retinal detachment.
27
RISK FACTORS :
1. Poor glycemic control, 2. Elevated blood pressure, 3. Hyperlipidemia.
PATHOGENESIS:
Diabetic retinopathy is because of the micro-vascular retinal changes.
Hyperglycemia induces thickening of the basement membrane by many mechanism which include increased expression of retinal intercellular adhesion molecule-1 (ICAM-1, nonenzymatic glycation, oxidative stress, protein kinase and the renin- angiotensin system,leading to incompetence of the vascular walls35. This influences several vasoactive factors and cytokines, such as vascular endothelial growth factor, interleukin-6. These damages change the formation of the blood-retinal barrier and also make the retinal blood vessels become more permeable. The hypoxia causes formation of fragile, new, blood vessels to grow along the retina and in vitreous humour. These newly formed blood vessels can bleed and cause clouding of vision, and also destroy the retina. Fibrovascular proliferation leads to tractional retinal detachment. neovascularisation also occurs in the angle of the anterior chamber of the eye and causes neovascular glaucoma.
28
FIGURE 8 – DIBETIC RETINOPATHY
CARDIOVASCULAR MORBIDITY AND MORTALITY
The very famous FRAMINGHAM HEART STUDY concluded saying increase in the incidence of heart failure, coronary heart disease, peripheral arterial disease and sudden death in diabetes patients. DM has been considered as “CHD risk equivalent”
by American heart association36,37. Synergism of increased glucose level with other cardiac risk factor, is the likely the cause of increase in cardiovascular morbidity and mortality rates. The other risk factors include hypertension, obesity, dyslipidemia, physical inactivity, and smoking. Type 2 DM patients have increased levels of PAI-1 (plasminogen activator inhibitor-1) & fibrinogen, which impairs fibrinolysis and enhance the coagulation process9.
29
GASTROINTESTINAL AND GENITOURINARY DYSFUNCTION
Gastroparesis and bowel motility alteration are the most common GI symptoms in patients with diabetes mellitus. Symptoms of gastroparesis include nausea, vomiting, abdominal bloating, early satiety. Chronic hyperglycemia causes dysfunction of parasympathetic nervous system and can impair gastric emptying.
Normal diarrhea is a feature of GI autonomic neuropathy related to diabetes9. The genitourinary abnormalities includes, erectile dysfunction,decreased sexual desire, decreased vaginal lubrication, dyspareunia.Diabetic cystopathy is defined as inability to sense the fullness of bladder& difficulty to void urine completely. Later progresses to symptoms like urinary hesitancy and incontinence9.
EFFECT OF DIABETES ON RESPIRATORY SYSTEM:
The lung complications of type 2 diabetes mellitus are mainly affecting the mechanical aspects of the organ39 .Diabetes affects connective tissue and microvasculature leading to pulmonary function abnormalities such as decreased vital capacity, decreasing compliance of the lung, TLC, decreased central and peripheral airflows38,40. Diabetes causes accelerated aging process, thickening of capillary endothelial basement membrane and alveoli, modification of surfactant and its function. This pulmonary microangiopathy leads to decreased diffusing capacity and endurance of respiratory musculature. And among the that the restrictive pattern of lung disease is the commonest one,
30
These effects are reported by using the spirometry and measuring the forced vital capacity and forced expiratory volume in first second and ratio between these two.
Figure 9. showing alveolar structure
SPIROMETRY & PFT:
Spirometry is the recording of lung volumes and capacities by using spirometer. It is a Simple test that Measures the flow, volumes, volume vs.Time of air flow. It is an easily available most useful pulmonary function test. It takes around only 10 to 15 minutes and carries almost no risk. It is the most used screening study. Other studies are being reserved for specific indications. The patient must be explained clearly about the procedure to reduce the errors. The test needs patients voluntary effort to inhale maximally beyond the tidal volume and exhale forcefully into the closed circuit.
31
Parameters that can be determined include:
- Forced expiratory volume in first second (FEV1) - Forced vital capacity (FVC)
- FEV1/FVC
- Forced expiratory flow 25%-75% (FEF25-75) Indications for Diagnosis:
1. Evaluate the patient having sudden onset of dyspnea, exertional dyspnea, chronic cough.
2. Screening of high risk populations.
3. Monitoring pulmonary toxicities of certain drugs.
4. Abnormalities in chest X ray, arterial blood gas analysis.
5. Pre-op evaluation.
6. Smokers more than 45 years (past & current) Indications for Prognosis:
1. Assessment of severity of illness.
2. Therapy response.
3. Planning of further treatment
32
4. Post Surgery improvement.
5. Disability assessment
Contraindications for spirometry:
Relative contraindications for spirometer includes recent heart disease Aortic aneurysm,
Recent eye surgery,
Active haemoptysis of unknown origin, Pneumothorax,
Cerebral artery aneurysm, Syncopal attacks.
33
PULMONARY FUNCTION TEST :
FIGURE 10 – LUNG VOLUME GRAPH
The most important spirometric data is the FVC, the patient inhales maximally, followed by exhaling completely as possible. Normally lungs can empty > 80 percent of their volume in 6 secs or less. The FEV1 is the volume of air which is exhaled in the 1st second of the FVC maneuver. The FEV1/FVC ratio is generally expressed as a percentage.
34
FIGURE 11 - NORMAL SPIROMETRY GRAPH
Normal spirometric flow diagram. (A) Flow-volume curve. (B) Volume-time curve. The smooth lines, expiratory time of greater than six seconds, and quick peak of the peak expiratory flow rate indicate a good spirometric effort41.
35
FIGURE 12: Flow-volume loop (Obstructive pattern)
Obstructive Disorders - The flow–volume curve can be used make the diagnosis of obstructive disorder. It has a distinct shape in such . These features include – The height of the curve (PEF) is much less than predicted.
The descending limb is concave (scooped), with the outward concavity being more pronounced with more severe obstruction.
The slope of the descending limb that represents MMEF and FEFs is reduced due to airflow limitation at low lung volumes.
36
FIGURE 13 - Flow-volume loop (Restrictive pattern)
Features of restrictive disorders
Most important features: ↓ FVC and normal or ↑ FEV 1 /FVC ratio
Other features: ↓ FEV 1 (proportional to FVC) but it can be normal ↓ PEF normal increased, or decreased Steep descending limb of FV
37
TABLE 1 – DIFFERNCE BETWEEN OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASE
COMMON CAUSES OF OBSTRUCTIVE AND RESTRICTIVE LUNG DISEASES
38
REVIEW OF HISTORICAL WORKS ON DIABETES AND ITS PULMONARY COMPLICATIONS
P.Lang et al conducted a cross sectional study covering about 11,763 subjects in Copenhagen city and documented the possible associations between Diabetes mellitus, plasma glucose and the spirometric values like FVC & FEV1. The study showed slight impairment in lung function which was more prominent in diabetic subjects, who were on insulin compared to those taking oral hypoglycaemic agents. It was finally concluded saying that both IDDM & NIDDM were having reduced lung functions since they had decreased FVC & FEV142.There are also many other studies which have reported decreased pulmonary capacity in diabetic patients due to changes in elastic properties of lungs.43,44,45,56
Davis et al conducted a large community-based study in Western Australia in type 2 diabetic patients and demonstrated that VC, FVC, FEV1, and PEF were decreased in type 2 diabetic patients. It was also suggested that the airflow limitation and reduced lung volumes and are likely to be chronic complications of type 2 diabetes47.
In Robert E. Walter et.al. study it was found that there was a progressive decrease in mean FVC values by about 109 ml/year 48.
A study which was conducted by Timothy M. Davis, revealed that there was an average decrease of 9.5% in mean FVC values in diabetics 49. They also showed that there was no correlation between HbA1c and spirometric measures, but there was a correlation with respect to duration of diabetes mellitus.
39
Walter.E.Robert et al showed the association between state of glycaemia and the pulmonary functions. It consisted of 87 members of Framingham and the result was reduction in FVC, FEV1 & FEV1/FVCRatio50.
A popular study carried out by Malcolm Sander Is lung a “target organ” in diabetes mellitus was. There is evidence of lung involvement in diabetic patients that is histopathologically proven ie.., by the process of alveolar epithelial thickening and thickening in the basal lamina of pulmonary capillaries highly suggesting the phenomenon of pulmonary microangiopathy51. Probably the alteration in lung tissue is due to the nonenzymatic glycosylation, which thereby causes decreased elastic recoiling of lung tissues. These changes finally leading to reduced lung volumes in diabetes mellitus.
Meo et al52,53 in their studies on Saudi diabetic patients showed significant reduction in FVC, FEV1, and PEF, as compared to their matched controls. They also showed a strong association with a dose–effect response of duration of disease and decreased pulmonary function impairment in their diabetic patients.
40
MATERIALS AND METHODS
STUDY POPULATION
This is a hospital based study. Study population include the patients who attend the diabetology OPD at Coimbatore medical college hospital, fulfilling the inclusion and exclusion criteria mentioned below. These are patients with diabetes who are attending the op for treatment.
SAMPLE SIZE
100 patients
DURATION OF STUDY: One year
(JANUARY 2018- DECEMBER 2018) INCLUSION CRITERIA
Type 2 diabetes mellitus patients Both male and female
Any duration of disease EXCLUSION CRITERIA
Patients having respiratory system complaints such as cough, sputum production , dyspnoea , fever.
Patients with gross abnormalities of vertebral column, thoracic cages.
41
Known cases of cardiac, respiratory, renal, musculoskeletal, other endocrine, major diseases.
Past history of abdominal surgeries , chest surgeries
Smokers, drug addictions.
STUDY DESIGN
Prospective study MODE OF EVALUATION
Informed written consent obtained from all patients chosen. They were handed over the questionnaire which contains a detailed personal, medical history of the patient. Routine basic medical examination of the patient was done which included recording of blood pressure, height, weight, BMI calculation. Any patient not meeting with the selection criteria were excluded from the study.
Blood sample would be collected to estimate FBS, HbA1C.
Patients were explained about the pulmonary function test , proper way of spirometric examination and the procedure of examination . Patients were then referred to the department of thoracic medicine to undergo pulmonary function test.
42
INVESTIGATIONS
PFT – FVC o FEV1 o FEV1/FVC
FBS
HbA1C
ETHICAL CLEARANCE
Obtained
CONFLICT OF INTEREST
NIL
DATA MANAGEMENT AND STATISTICAL ANALYSIS:
All data were analyzed using the statistical package for social science (SPSS) 10.0 for Windows program on the computer. The statistical significance was accepted as p value < 0.05. Using this software, frequencies, range, mean, standard deviation and ‘p’were calculated through Student‘t’ test, One way ANOVA, Pearson Correlation and Chi square test . P value of < 0.05 was taken as significant.
43
RESULTS
TABLE 2 : AGE DISTRIBUTION
CHART 1 - SHOWING AGE DISTRIBUTION
In our study the majority of the patients were between the age group of 40 – 60 years
32%
35%
26%
7%
AGE DISTRIBUTION
LESS THAN 50 51-60 61-70 MORE THAN 70
AGE IN YEARS NO OF PATIENTS PERCENTAGE
40- 50 32 32%
51-60 35 35%
61-70 26 26%
MORE THAN 70 7 7%
44
TABLE 3 - SEX DISTRIBUTION
CHART 2 – SHOWING SEX DISTRIBUTION
The study population had 51 % female and 49% male patients
51%
49%
SEX DISTRIBUTION
MALE FEMALE
SEX NO OF PATIENTS PERCENTAGE
MALE 51 51%
FEMALE 49 49%
45
TABLE 4 – DISTRIBUTION OF DURATION OF DISEASE
CHART 3 – SHOWING DISTRIBUTION OF DURATION OF DISEASE
The majority of the patients had the disease duration between 1 – 10 years
41%
45%
14%
DURATION OF DISEASE
< 5 YRS 5-10 YRS > 10 YRS
DURATION OF DISEASE NO OF PATIENTS PERCENTAGE
< 5 YRS 41 41%
5-10 YRS 45 45%
> 10 YRS 14 14%
46
TABLE 5 – DISTRIBUTION OF TYPE OF TREATMENT
TREATMENT NO OF PATIENTS PERCENTAGE
OHA 72 72%
INSULIN 28 28%
CHART 4 – SHOWING DISTRIBUTION OF TYPE OF TREATMENT
In our study population majority of patients were on OHA
72%
28%
TREATMENT
OHA INSULIN
47
TABLE 6 – DISTRIBUTION OF FASTING BLOOD SUGAR
CHART 5 – SHOWING DISTRIBUTION OF FBS
In our study most of the patients had FBS values between 120 – 180 mg/dl
8%
59%
17%
16%
FASTING BLOOD SUGAR
LESS THAN 120 120-180 180-220 MORE THAN 220
FASTING BLOOD SUGAR NO OF PATIENTS PERCENTAGE
LESS THAN 120 8 8%
120-180 59 59%
180-220 17 17%
MORE THAN 220 16 16%
48
TABLE 7- DISTRIBUTION OF HbA1C
CHART 6 – SHOWING DISTRIBUTION OF HbA1C
49 % of patients had HbA1 between 7.1 - 9
48%
49%
3%
HBA1C
LESS THAN 7 7.1-9 MORE THAN 9
HBA1C NO OF PATIENTS PERCENTAGE
5.5 - 7 48 48%
7.1-9 49 49%
MORE THAN 9 3 3%
49
TABLE 8 - DISTRIBUTION OF BODY MASS INDEX
CHART 7 – SHOWING DISTRIBUTION OF BODY MASS INDEX
Majority of the patients were of the BMI between 21- 25
19%
59%
22%
BODY MASS INDEX
LESS THAN 20 21-25 MORE THAN 25
BODY MASS INDEX NO OF PATIENTS PERCENTAGE
LESS THAN 20 19 19%
21-25 59 59%
MORE THAN 25 22 22%
50
TABLE 9 – DISTRIBUTION OF FVC % PREDICTED
CHART 8 – SHOWING DISTRIBUTION OF FVC% PREDICTED
In our study 93 % of the patients had FVC < 80% indicating a restrictive type of lung disease .
7%
93%
FVC (% PREDICTED)
> 80% < 80%
FVC % PREDICTED NO OF PATIENTS PERCENTAGE
> 80% 7 7%
< 80% 93 93%
51
TABLE 10 – DISTRIBUTION OF FEV1/FVC % PREDICTED
CHART 9 – SHOWING DISTRIBUTION OF FEV1/FVC % PREDICTED
Majority of patients had the FEV1/FVC (% PREDICTED) > 80 % favouring a restrictive type of lung disease
92%
8%
FEV1/FVC (% PREDICTED)
> 80% < 80%
FEV1/FVC % PREDICTED NO OF PATIENTS PERCENTAGE
> 80% 92 92%
< 80% 8 8%
52
TABLE 11 – DISTRIBUTION OF PATTERN OF IMPAIRMENT OF LUNG FUNCTION
CHART 10- SHOWING DISTRIBUTION OF PATTERN OF IMPAIRMENT OF LUNG FUNCTION
In our study around 49 % had mild restriction and 30 % had moderate restrictive type of lung disease, 7 % had normal lung function.
7%
30% 49%
14%
PATTERN OF IMPAIRMENT OF PULMONARY FUNCTION
NORMAL MILD MODERATE SEVERE
IMPRESSION NO OF PATIENTS PERCENTAGE
NORMAL 7 7%
MILD RESTRICTION 49 49%
MODERATE RESTRICTION 30 30%
SEVERE RESTRICTION 14 14%
53
TABLE 12 – CORRELATION OF FVC % PREDICTED WITH FBS
FASTING BLOOD SUGAR
FVC(% PREDICTED)
MEAN SD
LESS THAN 120 79.25 4.52
120-180 68.81 9.96
180-220 61.12 7.21
MORE THAN 220 56.13 8.22
P VALUE - 0.001 SIGNIFICANT
ANOVA
54
CHART 11 - SHOWING CORRELATION OF FVC % PREDICTED WITH FBS
In our study there was a significant reduction in the FVC in patients with higher FBS values.
.
79.25
68.81
61.12
56.13
LESS THAN 120 120-180 180-220 MORE THAN 220
FBS VS FVC
LESS THAN 120 120-180 180-220 MORE THAN 220
55
TABLE 13 – CORELLATION OF FEV1 % PREDICTED AND FBS
FASTING BLOOD SUGAR
FEV1(%predicted)
MEAN SD
LESS THAN 120 82.75 4.86
120-180 75.05 4.81
180-220 71.82 4.89
MORE THAN 220 68.68 5.45
P VALUE - 0.019 SIGNIFICANT
ANOVA
56
CHART 12 - SHOWING CORRELATION OF FEV1 % PREDICTED WITH FBS
FBS AND FEV1 % PREDICTED had strong negative correlation. Significant reduction in the fev1 % predicted with increasing fasting blood sugar levels.
82.75
75.05
71.82
68.68
LESS THAN 120 120-180 180-220 MORE THAN 220
FBS VS FEV1% PREDICTED
LESS THAN 120 120-180 180-220 MORE THAN 220
57
TABLE 14 – CORRELATION OF FEV1/FVC (% PREDICTED) WITH FBS
FASTING BLOOD SUGAR
FEV1/FVC(% PREDICTED)
MEAN SD
LESS THAN 120 96 6.51
120-180 109.81 17.91
180-220 117.82 13.47
MORE THAN 220 123.68 15.95
P VALUE - 0.001 SIGNIFICANT
ANOVA
58
CHART13 - SHOWING CORRELATION OF FEV1/FVC (% PREDICTED) WITH FBS
In our study there was decrease in FVC and FEV1 but decrease in FVC was more than fev1 hence there was increase in FEV1/FVC which has positive correlation with FBS ,indicating a more severe restrictive pattern
96
109.81
117.82
123.68
LESS THAN 120 120-180 180-220 MORE THAN 220
FBS VS FEV1/ FVC % PREDICTED
59
TABLE 15 – CORRELATION OF FVC % PREDICTED WITH HbA1C
HBA1C
FVC (% PREDICTED)
MEAN SD
LESS THAN 7 72.25 9.48
7.1-9 61.37 8.73
MORE THAN 9 52 9.64
P VALUE - 0.001
SIGNIFICANT
ANOVA
60
CHART 14 – SHOWING CORELATION OF FVC % PREDICTED WITH HbA1C
With poor control of diabetes there was progressive decrease in the FVC which was statistically significant in our study.
72.25
61.37
52
LESS THAN 7 7.1-9 MORE THAN 9
HBA1C VS FVC % PREDICTED
61
TABLE 16 – CORRELATION OF FEV1 % PREDICTED WITH HbA1C
HBA1C
FEV1(% PREDICTED)
MEAN SD
LESS THAN 7 77.58 4.67
7.1-9 71.16 5.16
MORE THAN 9 66.33 7.21
P VALUE - 0.021 SIGNIFICANT
ANOVA
62
CHART 15 – SHOWING CORELATION OF FEV1 % PREDICTED WITH HbA1C
FEV1 % PREDICTED was progressive decrease with increase in HbA1C values.
77.58
71.16
66.33
LESS THAN 7 7.1-9 MORE THAN 9
HBA1C VS FEV1 %PREDICTED
LESS THAN 7 7.1-9 MORE THAN 9
63
TABLE 17 – CORRELATION OF FEV1/FVC (% PREDICTED) WITH HbA1C
HBA1C
FEV1/FVC(% PREDICTED)
MEAN SD
LESS THAN 7 105.61 16.96
7.1-9 117.08 16.43
MORE THAN 9 128.66 9.53
P VALUE - 0.001 SIGNIFICANT
ANOVA
64
CHART 16 – GRAPH SHOWING CORELLATION OF FEV1/FVC (% PREDICTED) WITH HbA1C
There was a positive correlation between all levels of HbA1C and FEV1/FVC % predicted indicating more sever restriction with poorer diabetic control.
105.61
117.08
128.66
LESS THAN 7 7.1-9 MORE THAN 9
HBA1C VS FEV1/FVC % PREDICTED
65
TABLE 18 – CORELATION OF FVC % PREDICTED WITH
DURATION OF DISEASE
DURATION OF DISEASE
FVC(% PREDICTED)
MEAN SD
< 5 YRS 73.54 7.89
5-10 YRS 63.38 8.65
> 10 YRS 54.57 10.12
P VALUE - 0.001 SIGNIFICANT
ANOVA
66
CHART 17 – SHOWING CORELATION OF FVC % PREDICTED
WITH DURATION OF DISEASE
With increasing duration of diabetes there was progressive decline in the FVC which was statistically significant in our study.
73.54 63.38
54.57
< 5 YRS 5-10 YRS
> 10 YRS
DURATION VS FVC
67
TABLE 19 – CORELATION OF FEV1 % PREDICTED WITH
DURATION OF DISEASE
DURATION OF DISEASE
FEV1(%)
MEAN SD
< 5 YRS 78.78 6.88
5-10 YRS 71.86 4.29
> 10 YRS 67.57 4.86
P VALUE - 0.013 SIGNIFICANT
ANOVA
68
CHART 18 – SHOWING CORRELATION OF FEV1 % PREDICTED WITH DURATION OF DISEASE
With increasing duration of diabetes there was progressive decline in the FEV1 which was statistically significant in our study.
78.78 71.86
67.57
< 5 YRS 5-10 YRS
> 10 YRS
DURATION VS FEV1
69
TABLE 20 – CORRELATION OF FEV1/FVC (% PREDICTED) WITH DURATION OF DISEASE
DURATION OF DISEASE
FEV1/FVC % PREDICTED
MEAN SD
< 5 YRS 104.43 15.53
5-10 YRS 114.28 16.08
> 10 YRS 126.21 10.13
P VALUE - 0.001 SIGNIFICANT
ANOVA
70
CHART 19 - SHOWING CORRELATION OF FEV1/FVC (% PREDICTED) WITH DURATION OF DISEASE
With increasing duration of the disease there was a progressive restrictive pattern of lung disease, patients with duration of disease more than 10 years had more severe disease.
104.43 114.28
126.21
< 5 YRS 5-10 YRS
> 10 YRS
DURATION VS FVC/FEV1 % PREDICTED
71
TABLE 21 – DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH DURATION OF DISEASE
IMPRESSION
DURATION
< 5 YRS 5-10 YRS > 10 YRS
NORMAL 7 0 0
MILD RESTRICTION 26 21 2
MODERATE RESTRICTION 7 18 5
SEVERE RESTRICTION 1 6 7
KRUSKAL WALLIS TEST P VALUE - 0.001
SIGNIFICANT
72
CHART 20 – SHOWING THE DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH DURATION OF DISEASE
In our study the patients with normal lung function all of them belonged to group of lesser duration of disease < 5 years while around 50 % of the severe restrictive pattern had disease for longer duration. With kruskal wallis test it was statistically significant.
100%
0% 0%
53%
43%
4%
23%
60%
17%
7%
43%
50%
< 5 YRS 5-10 YRS > 10 YRS
DURATION VS DEGREE OF IMPAIRMENT OF LUNG FUNCTION
NORMAL MILD MODERATE SEVERE
73
TABLE 22–CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH HBA1C
IMPRESSION
HBA1C
< 7% 7.1-9% > 9%
NORMAL 7 0 0
MILD 32 17 0
MODERATE 6 23 1
SEVERE 3 9 2
KRUSKAL WALLIS TEST P VALUE - 0.001
SIGNIFICANT
74
CHART 21 – SHOWING CORELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH HbA1C
With kruskal wallis test it was found that people with poorer diabetic control indicated by high HbA1C had more severe restriction.
100%
0% 0%
65%
35%
0%
20%
76%
4%
21%
64%
15%
< 7% 7.1-9% > 9%
HBA1C VS DEGREE OF IMPAIRMENT OF LUNG FUNCTION
NORMAL MILD MODERATE SEVERE
75
TABLE 23 – CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH FBS
IMPRESSION
FASTING BLOOD SUGAR
< 120 120-180 180-220 > 220
NORMAL 3 4 0 0
MILD 5 39 3 2
MODERATE 0 11 11 8
SEVERE 0 5 3 6
KRUSKAL WALLIS TEST P VALUE - 0.001
SIGNIFICANT
76
CHART 22 – SHOWING CORRELATION OF DEGREE OF IMPAIRMENT OF LUNG FUNCTION WITH FBS
In our study it was noted that patients with lower FBS values had only mild restrictive disease, kruskal wallis test was applied and it was statistically significant.
43%
57%
0% 0%
10%
80%
6% 4%
0%
37% 37%
26%
0%
18%
27%
55%
< 120 120-180 180-220 > 220
FBS VS DEGREE OF IMPAIRMENT OF LUNG FUNCTION
NORMAL MILD MODERATE SEVERE
77
DISCUSSION AND CONCLUSION
The study was conducted in 100 diabetic patients. Most of the patients (67%) in our study group was between the age of 40-60years. 51 % were male and 49% were female patients. around 86% of the patient had disease duration between 1 – 10 years.
It was found that diabetics develop restrictive type of lung disease. The pulmonary function test done showed around 49 % of them had mild restrictive pattern. In our study none of the diabetics had obstructive lung disease.
There was reduction in FVC % PREDICTED and FEV1 %PREDICTED. With poorer diabetic control as revealed by higher FBS and HbA1C levels, the reduction is more indicating a negative correlation. The mean FVC %PREDICTED for patient with FBS >220 mg/dl was around 56.13% while for patients with FBS < 120 mg/dl was 79.25%. Patients with HbA1C > 9 had an mean FVC %PREDICTED of 52 % .
As the duration of diabetes increases there was a progressive fall in FVC
%PREDICTED, FEV1% PREDICTED and FEV1/FVC % PREDICTED.
The cause for the underlying mechanisms for the restrictive pattern of lung functions in diabetics done in previous studies, include glycosylation bronchial tree proteins, pulmonary alveolar microangiopathy and increased cross-linkage formation between polypeptides of collagen in pulmonary connective tissue, which decrease FVC and thus responsible for restrictive respiratory defects54, thickening of basal lamina 55, and increased susceptibility to respiratory infections 56.
The results were in accordance with the previous studies.
78
LIMITATIONS OF THE STUDY:
It is a single centre study.
Study population was less – 100 patients.
Diabetes with other comorbid conditions were not included in the study but that is the common finding in Indian scenario.
.
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