Anandakumar Amutha

Clinical profile of diabetes in the young seen between 1992 and 2009 at a specialist diabetes centre in south India

AIM To describe the trends and clinical profile of young diabetic patients (YD) attending a tertiary diabetes centre in south India. METHODS We reviewed medical records of 2630 YD patients (age at onset ≤25 years) registered between 1992 and 2009. Patients were classified as type 1 diabetes (T1DM), type 2 diabetes (T2DM) gestational diabetes mellitus (GDM) and other types. Retinopathy was assessed initially by direct and indirect ophthalmoscopy and later by retinal photography, nephropathy if urine protein excretion was >500 mg/day, neuropathy if vibration perception threshold on biothesiometry was ≥20 V. RESULTS The percentage of YD patients rose from 0.55% in 1992 to 2.5% in 2009 (trend chi square, 15.1, p<0.001). Of the 2630 YD subjects registered, 1135 (43.2%) had T1DM, 1262 (48.0%) had T2DM, 118 (4.5%) had GDM and 115 (4.4%) other types. T1DM patients were younger, had lower body mass index, waist circumference, systolic and diastolic blood pressures, and less family history of diabetes compared to T2DM (p<0.001 for each). Retinopathy was seen in 71.9% and 77.3% nephropathy in 22.1% and 12.1% and neuropathy in 34.5% and 21.4% of T2DM and T1DM respectively in those with ≥15 years duration of diabetes. CONCLUSIONS The percentage of YD in south India is increasing, predominantly due to early onset T2DM.

Associations of β-Cell Function and Insulin Resistance with Youth-Onset Type 2 Diabetes and Prediabetes Among Asian Indians

AIM This study examined β-cell function and insulin resistance (homeostasis model assessment-insulin resistance [HOMA-IR]) in Asian Indian youth with type 2 diabetes mellitus (T2DM-Y) and prediabetes. SUBJECTS AND METHODS Eighty-two subjects with non-insulin-requiring type 2 diabetes and age of onset below 25 years were recruited within 18 months of diagnosis and compared with age- and sex-matched subjects with prediabetes (n=31) and normal glucose tolerance (NGT) (n = 83). Body mass index (BMI) and waist circumference were measured, and blood samples were taken in the fasting state and after 30, 60, 90, and 120 min of an oral glucose load for assessment of plasma glucose and insulin levels. Insulin sensitivity/resistance measures was calculated by using the reciprocal of the fasting insulin, the HOMA-IR equation, and the composite whole body insulin sensitivity index (Matsuda Index), and β-cell function was calculated by the oral disposition index (DIo). RESULTS T2DM-Y and prediabetes subjects had higher BMI, waist circumference, and fasting insulin than NGT subjects (P<0.05 for each). The 30-min insulin levels were lower in T2DM-Y and higher in prediabetes subjects compared with NGT (57 and 140 vs. 129 μIU/mL, P<0.001). The T2DM-Y group had greater insulin resistance (HOMA-IR, 1.87 vs. 0.97; P<0.05) and lower β-cell function (DIo, 0.36 vs. 3.28; P<0.001) than NGT. In separate models, the Matsuda Index and DIo were independently associated with prediabetes and T2DM-Y (P<0.05). However, when both were included together, only DIo remained associated with T2DM-Y, whereas both DIo and Matsuda Index were associated with prediabetes (P<0.05). When controlled for adiposity (BMI and waist circumference), an association was observed but in opposite directions, with waist being positively associated with prediabetes (P = 0.016) and BMI negatively associated with T2DM-Y (P = 0.009). CONCLUSIONS Among Asian Indians, β-cell dysfunction appears to be more strongly associated with T2DM-Y than insulin resistance.

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset Type 1 and Type 2 Diabetes

AIM To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). METHODS T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. RESULTS The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. CONCLUSION Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR.

Clinical Profile and Complications of Childhood- and Adolescent-Onset Type 2 Diabetes Seen at a Diabetes Center in South India

OBJECTIVE This study describes the clinical characteristics of childhood- and adolescent-onset type 2 diabetes mellitus (CAT2DM) seen at a diabetes center in southern India. RESEARCH DESIGN AND METHODS Between January 1992 and December 2009, 368 CAT2DM patients were registered. Anthropometric measurements were done using standardized techniques. Biochemical investigations included C-peptide measurements and glutamic acid decarboxylase antibody assay wherever feasible. Retinopathy was diagnosed by retinal photography; microalbuminuria, if urinary albumin excretion was between 30 and 299 mg/μg of creatinine; nephropathy, if urinary albumin excretion was ≥300 mg/μg; and neuropathy, if vibration perception threshold on biothesiometry was ≥20 V. RESULTS The proportion of CAT2DM patients, expressed as percentage of total patients registered at our center, rose from 0.01% in 1992 to 0.35% in 2009 (P<0.001). Among the 368 cases of CAT2DM, 96 (26%) were diagnosed before the age of 15 years. The mean age at first visit and age at diagnosis of the CAT2DM subjects were 22.2±9.7 and 16.1±2.5 years, respectively. Using World Health Organization growth reference charts, 56% of boys and 50.4% of girls were >85(th) percentile of body mass index for age. Prevalence rates of retinopathy, microalbuminuria, nephropathy, and neuropathy were 26.7%, 14.7%, 8.4%, and 14.2%, respectively. Regression analysis revealed female gender, body mass index >85(th) percentile, parental history of diabetes, serum cholesterol, and blood pressure to be associated with earlier age at onset of CAT2DM. CONCLUSIONS CAT2DM appears to be increasing in urban India, and the prevalence of microvascular complications is high. Female predominance is seen at younger ages.

Diabetes complications in childhood and adolescent onset type 2 diabetes-a review.

Diabetes mellitus is one of the most common endocrine disorders in children. Earlier, diabetes in children was almost exclusively type 1 diabetes. Recently, the scenario has changed and increasing numbers of children and adolescent T2DM are being diagnosed. As the epidemic of T2DM shifts to children and adolescents, there is an increased risk of development of micro and macrovascular complications. This could potentially affect the economy of the nation apart from posing a large burden to the individual and his or her family. Prevention and treatment are especially important, given the fact that onset at an early age increases the risk of developing micro and macrovascular complications due to increased duration of exposure to hyperglycemia and other metabolic abnormalities. Diagnosing children and adolescents with T2DM early and instituting good control of all risk factors could yield good results in the prevention of long term complications of diabetes. This review focuses on the prevalence of complications of diabetes among children and adolescents with T2DM.

A single-center, open, comparative study of the effect of using self-monitoring of blood glucose to guide therapy on preclinical atherosclerotic markers in type 2 diabetic subjects.

Background: The aim of our study was to determine the effect of treatment based on preprandial and postprandial self-monitoring of blood glucose (SMBG) on the progression of carotid intima-medial thickness (CIMT) in noninsulin-treated type 2 diabetes mellitus (T2DM) subjects. Methods: In this 18-month prospective trial, we recruited subjects 18–70 years of age, treated with metformin and sulfonylurea, with a standardized hemoglobin A1c (HbA1c) level ⩽9.0%. Subjects were randomized to use of fasting/preprandial (FP) SMBG results to adjust evening medication or use of postprandial (PP) SMBG results to adjust morning medication. The primary end point was change in CIMT; change in HbA1c was a secondary end point. Results: Of the 300 subjects randomized, 280 (140 in each group) completed all biochemical tests and CIMT analysis. Carotid intima-medial thickness was reduced significantly in PP subjects from 0.78 (±0.15) mm to 0.73 (±0.14) mm (p < 0.005), but no significant CIMT reduction was seen in FP subjects. A significant reduction in HbA1c was also seen in the PP group (p < 0.005) but not in the FP group 1 (p = 0.165). significant improvements in body mass index (p = 0.038), waist circumference (p < 0.001), systolic blood pressure (p = 0.008), and serum cholesterol (p = 0.02) were also seen in PP subjects but not in FP subjects. Conclusion: Use of postprandial SMBG data to adjust therapy was associated with a significant regression of carotid intima-medial thickening and a reduction in HbA1c in T2DM, whereas no significant improvement in these parameters was seen in subjects who used fasting/preprandial SMBG data for therapy adjustment.

Relationship of betatrophin with youth onset type 2 diabetes among Asian Indians

BACKGROUND AND AIMS Betatrophin is emerging as a marker for compensatory beta cell proliferation. While betatrophin has been mainly investigated in adults, there is a lack of data on betatrophin levels in youth-onset type 2 diabetes mellitus (T2DM-Y). The aim of this study was to determine levels of betatrophin and its association with T2DM-Y in Asian Indian participants. METHODS We recruited 100 individuals with normal glucose tolerance (NGT; n=50) and newly-diagnosed cases (within 18 months of first diagnosis) of T2DM-Y (n=50) with onset between 12 and 24 years of age from a large tertiary diabetes center in Chennai in southern India. Insulin resistance was measured by homeostatic model (HOMA-IR) and insulin secretion by oral disposition index (DIO). Betatrophin levels were measured by enzyme-linked immunosorbent assay. RESULTS Betatrophin levels were significantly lower in the T2DM-Y group compared with the NGT group (803 vs 1104 pg/ml, p<0.001). Betatrophin showed a significant inverse correlation with waist circumference (p=0.035), HOMA-IR (p<0.001), fasting and 2 h postprandial glucose (p<0.01), glycated hemoglobin (p=0.019) and a positive correlation with fasting C-peptide (p<0.001) and DIO (p=0.012). In regression analysis, betatrophin was independently associated with T2DM-Y even after adjustment for age, gender, and waist circumference (OR per standard deviation: 0.562, 95% CI: 0.342-0.899, p=0.019). However, the association was lost when HOMA-IR was included in the model (OR: 1.141, 95% CI: 0.574-2.249; p=0.646). CONCLUSION Betatrophin levels are lower in T2DM-Y and this association is likely mediated through insulin resistance.

Association of glycated hemoglobin with carotid intimal medial thickness in Asian Indians with normal glucose tolerance

AIM To assess the association of glycated hemoglobin (HbA1c) levels with carotid intimal medial thickness (CIMT) in Asian Indians with normal glucose tolerance (NGT). METHODS Subjects with NGT were recruited from the Chennai Urban Rural Epidemiology Study carried out on a representative population of Chennai, South India. All subjects had fasting plasma glucose <100 mg/dl (5.6 mmol/l) and 2-h post load plasma glucose <140 mg/dl (7.8 mmol/l). HbA1c was measured using the Biorad Variant machine. CIMT was measured on the right common carotid artery using high-resolution B-mode ultrasonography. RESULTS The study group included 1383 NGT subjects, of whom 760 (54.9%) were women. The mean CIMT value in the 1st quartile of HbA1c (<5.2%) was 0.65 and it increased significantly to 0.73 in the last quartile of HbA1c (>5.8) (p<0.001). Regression analysis showed that HbA1c had a strong association with CIMT after adjusting for age, gender, waist circumference, systolic and diastolic blood pressure, LDL cholesterol, serum triglycerides, HOMA-IR and smoking (ß - 0.046, p=0.047). CONCLUSION Even among subjects with NGT, there is a significant increase in CIMT with increasing levels of HbA1c, showing the value of using HbA1c for diagnosis of glucose intolerance.

Incidence of complications in young-onset diabetes: Comparing type 2 with type 1 (the young diab study)

BACKGROUND There is little data on the incidence of diabetes complications in young onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in non European populations. METHODS From a tertiary diabetes centre, Chennai, India, we recruited 108 T1DM (defined by abrupt onset of symptoms or diabetic ketoacidosis, absent insulin reserve requiring insulin treatment) and 90 T2DM participants (defined by absence of ketosis, good beta-cell reserve, and good response to oral agents) who were diagnosed between the ages of 10 and 25years, and without any evidence of diabetes complications at diagnosis. We estimated the incidence of various complications (median follow up of five years); retinopathy was defined by presence of at least one definite microaneurysm by retinal photography, nephropathy by urinary albumin excretion ⩾30μg/mg of creatinine, neuropathy by vibration perception threshold ⩾20V on biothesiometry, peripheral vascular disease by an ankle-brachial index <0.9, and ischemic heart disease (IHD) by history of myocardial infarction or coronary revascularization or Q waves on ECG or on drug treatment for IHD. RESULTS The mean ages at diagnosis of T1DM and T2DM participants were 17.1±4.2vs. 21.6±3.6years respectively. The incidence of various complications reported in numbers/1000 person years of follow up of T1DM and T2DM were: retinopathy 77.4vs. 78.0/1000 person years, nephropathy, 62.0vs. 58.8, neuropathy 7.8 vs. 13.9 and ischemic heart disease 1.2vs. 5.4. In Cox regression analysis, after adjustment for age, glycated hemoglobin, systolic blood pressure and serum cholesterol, T2DM participants had 2.11 times (95%CI: 1.27-3.51) higher risk of developing any diabetes complication, compared to T1DM. CONCLUSIONS Young-onset T2DM have a more aggressive disease course than T1DM.

Comparison of Characteristics Between Nonobese and Overweight/Obese Subjects with Nonalcoholic Fatty Liver Disease in a South Indian Population

AIMS This study was designed to compare the characteristics of nonobese and overweight/obese subjects with nonalcoholic fatty liver disease (NAFLD) in an urban South Indian population. SUBJECTS AND METHODS The study group comprises 541 subjects drawn from the Chennai Urban Rural Epidemiology Study (CURES), which was carried out on a representative sample of Chennai city in southern India. NAFLD was diagnosed by ultrasonography. Subjects with NAFLD were classified as nonobese (body mass index of ≤22.9 kg/m(2)) and overweight/obese (body mass index of ≥23 kg/m(2)) based on World Health Organization Asia Pacific guidelines. Coronary artery disease (CAD) was assessed by a resting 12-lead electrocardiogram that was Minnesota-coded. Insulin resistance was assessed by using the homeostasis assessment model (HOMA-IR) using the following formula: fasting insulin (μIU/mL)×fasting glucose (mmol/L)/22.5. RESULTS In total, 173 of 541 (32%) subjects had NAFLD, of whom 48 (27.7%) had nonobese NAFLD and 125 (72.3%) had overweight/obese NAFLD. Compared with overweight/obese NAFLD patients, fasting blood glucose (104±29 vs. 119±45 mg/dL; P<0.05) and HOMA-IR (2.1±1.8 vs. 2.9±1.8; P<0.001) were lower and high-density lipoprotein cholesterol (43±9 vs. 39±8 mg/dL; P<0.001) was higher among nonobese NAFLD subjects. Multiple logistic regression analysis showed a significant association between nonobese NAFLD and CAD (P=0.013) even after adjusting for age, diabetes, hypercholesterolemia, HOMA-IR, and hypertension. CONCLUSIONS This study suggests that even nonobese NAFLD subjects have an association with CAD.