How should developing countries manage diabetes?
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Cost of Illness↗
Biomedical subjects
Ambady Ramachandran
Publications and source records attributed to Ambady Ramachandran.
High incidence of glucose intolerance in Asian-Indian subjects with acute coronary syndrome.
OBJECTIVE: The risk of diabetes and coronary heart disease is high in Asian Indians. In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS. RESEARCH DESIGN AND METHODS: A total of 146 nondiabetic subjects (121 men, 25 women) with ACS admitted to two hospitals in 1 year were enrolled. Random blood glucose at admission and a standard oral glucose tolerance test within 3 days were done. Glucose tolerance was categorized as normal glucose tolerance, impaired glucose tolerance (IGT) or impaired fasting glucose, and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HbA1c [A1C] >6.0%) or possibly stress diabetes (A1C <6.0%). Subjects not on antidiabetic treatment were reassessed with a glucose tolerance test between 1 and 2 months. Fasting plasma specific insulin, proinsulin, their molar ratios, and insulin resistance (homeostasis model assessment) were estimated at baseline. RESULTS: Mean age of the cohort was 55 +/- 10.6 (SD) years. At baseline, 24 (16.4%) had normal glucose tolerance, 67 (45.9%) had IGT or impaired fasting glucose, and 55 (37%) had diabetes (35 [24%] were undiagnosed and 20 [13.7%] had stress diabetes). At follow-up, 53 of 92 responders (57.6%) continued to have IGT or diabetes. Mean baseline plasma insulin, proinsulin and its ratios, and insulin resistance were higher than normal in all subgroups. CONCLUSIONS: Nondiabetic Asian Indians showed a high prevalence of hyperglycemia following ACS. ACS was associated with insulin resistance and increased levels of specific insulin, proinsulin, and high proinsulin-to-insulin ratios.
Acute Disease↗
Prevention of type 2 diabetes: issues and strategies for identifying persons for interventions.
Because of the ongoing worldwide diabetes epidemic and new evidence that type 2 diabetes can be prevented or delayed, we are compelled to implement prevention efforts. Health policy makers need to bridge the evidence gap left by prevention trials that did not include all groups at risk for developing diabetes. Intensive interventions may be appropriate for groups with similar risk as those studied in clinical trials, while less intense efforts may be considered for those groups that have not been studied. Factors such as structure of the health care system and individual social and economic situations may influence the implementation of prevention efforts. Currently, no universally validated and well-tested method exists to identify all people at high risk for developing diabetes. However, groups that will be targeted for prevention efforts can be identified through several reasonable strategies.
Clinical Trials as Topic↗
Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population.
The neurogenic differentiation-1 (NEUROD1), neurogenin-3 (NEUROG3), and hepatic nuclear factor-1alpha (TCF1) genes are interacting transcription factors implicated in controlling islet cell development and insulin secretion. Polymorphisms of these genes (Ala45Thr [NEUROD1], Ser199Phe [NEUROG3], and Ala98Val [TCF1]) have been postulated to influence the development of type 2 diabetes. We have investigated the role and interaction between these variants using PCR/restriction fragment-length polymorphism assays in 454 subjects recruited as part of a population survey in South India. Additionally, 97 South Indian parent-offspring trios were studied. Polymorphisms of all three genes were associated with either fasting blood glucose (FBG) and/or 2-h blood glucose (BG) in either the total dataset or when restricted to a normoglycemic population. A monotonically increasing effect, dependent on the total number of risk-associated alleles carried, was observed across the whole population (P < 0.0001 for FBG and 2-h BG), raising FBG by a mean of 2.9 mmol/l and 2-h BG by a mean of 4.3 mmol/l. Similarly, an ascending number of the same risk alleles per subject increased the likelihood of type 2 diabetes (P = 0.002). In conclusion, we observed a combined effect of variations in NEUROD1, NEUROG3, and TCF1 in contributing to overall glucose intolerance in a South Indian population.
Amino Acid Substitution↗
Effectiveness of different types of footwear insoles for the diabetic neuropathic foot: a follow-up study.
OBJECTIVE: To compare the effectiveness of different types of footwear insoles in the diabetic neuropathic foot. RESEARCH DESIGN AND METHODS: A sample of 241 consecutive diabetic patients (158 men and 83 women, age 57.5 +/- 9.6 years [mean +/- SD], and mean duration of diabetes 12.3 +/- 7.2 years) attending the foot clinic with previous foot ulceration and those considered at high risk of foot ulceration were included in the study. The study groups consisted of group 1, patients provided with sandals with insoles made with microcellular rubber (n = 100); group 2, with sandals with polyurethane foam (n = 59); group 3, with molded insoles (n = 32); and group 4, with their own footwear containing leather board insoles (n = 50). Neuropathy status was assessed using a biothesiometer. Plantar pressure was measured using the RS Scan inshoe pressure measurement system. Data obtained from the metatarsal heads were used as the peak pressure. The state of the sandals was assessed after 9 months. The patients were considered to have had an ulcer relapse when either a new ulcer appeared at the site of a previous one or a new foot ulcer appeared in a different area. RESULTS: Patients who were using therapeutic footwear showed lower foot pressure (group 1, 6.9 +/- 3.6; group 2, 6.2 +/- 3.9; and group 3, 6.8 +/- 6.1 kPa; P = 0.0001), while those who used the nontherapeutic footwear showed an increased foot pressure (group 4, 40.7 +/- 20.5 kPa; P = 0.008). The occurrence of new lesions was significantly higher in patients in group 4 (33%) when compared with that of all other groups (4%). CONCLUSION: Therapeutic footwear is useful to reduce new ulceration and consequently the amputation rate in the diabetic population.
Diabetic Angiopathies↗
Nerve conduction abnormalities in different stages of glucose intolerance.
AIMS: To look for changes in nerve conduction velocity (NCV) in early stages of glucose intolerance, i.e. in impaired glucose tolerance (IGT) and in asymptomatic newly diagnosed Type 2 diabetic subjects (NDD). MATERIALS AND METHODS: A total of 225 subjects were categorized as: Group 1: Subjects with normal glucose tolerance (NGT), Group 2: IGT subjects and Group 3: NDD subjects. Motor (MCV) and Sensory nerve Conduction Velocity (SCV) measurements were done. RESULTS: The mean MCV was significantly lower in the NDD group (47 +/- 5 m/s) when compared with the other two groups (IGT=50 +/-4.5 m/s; NGT= 53 +/- 4 m/s; P=0.0001). The IGT group of subjects also exhibited a significantly lower mean MCV when compared with the NGT subjects (P=0.0001). The mean SCV in the NDD group (42+10 m/s) was also significantly lower (P< 0.0007) than the NGT (46+6 m/s) and the IGT (48+10 m/s) groups. No significant difference in the mean SCV between the NGT and IGT groups was noted. In the multiple linear regression analysis both age and male gender were the risk factors for abnormal MCV and SCV. Abnormal MCV was found to be associated with 2-hr post glucose levels (R2 = 14.5%), while HbA1c (R2 = 4.9%) contributed towards abnormal SCV. CONCLUSION: Abnormal NCV is a common finding in NDD subjects. Slower mean MCV demonstrated by IGT subjects, calls for early screening of these subjects for complications.
Adult↗
Plasma adiponectin is an independent predictor of type 2 diabetes in Asian indians.
OBJECTIVE: Adiponectin, secreted by fat cells, has regulatory functions on energy metabolism. Its low levels are predictive of future development of diabetes. Because no studies on the regulatory role of adiponectin in glucose homeostasis in Asian Indians exist, this analysis was performed to determine the prospective association of adiponectin and diabetes in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Baseline values of plasma adiponectin, results of anthropometry, fasting and 2-h plasma glucose levels, HbA(1c), results of lipid profile, and insulin resistance were analyzed in 91 subjects with IGT (53 men and 38 women) in a primary prevention study. Reassessment of glucose tolerance was performed during 1-year review. The predictive nature of adiponectin for development of diabetes was assessed using univariate and multiple logistic regression analyses. A control group comprising healthy, normoglycemic individuals was used for comparison. RESULTS: At follow-up, diabetes had developed in 25 of the 91 study subjects. The mean baseline adiponectin level was lower in the diabetic subjects than in the nondiabetic subjects (11.3 +/- 5.5 vs. 16.7 +/- 7.6 micro g/ml, P = 0.0017). Low adiponectin level was a strong predictor of future development of diabetes, and HbA(1c) also showed a positive predictive association. Women had higher adiponectin levels (16.4 +/- 6.1 micro g/ml) than men (13.9 +/- 7.6 micro g/ml) (P = 0.035). CONCLUSIONS: In Asian Indians, low plasma adiponectin level was predictive of future development of diabetes.
Adiponectin↗
Type 2 diabetes in Asian-Indian urban children.
OBJECTIVE: Due to a background of high prevalence of type 2 diabetes and the increasing rate of obesity occurring in relatively young urban children, we felt the need to look for type 2 diabetes in children. RESEARCH DESIGN AND METHODS: A study of cases of type 2 diabetes with age at diagnosis of </=15 years seen at a diabetes speciality center in Chennai, India, is reported. A total of 18 children (5 boys and 13 girls) aged 9-15 years with insidious onset of diabetes responding to oral antidiabetic agents (ODAs) for periods from 2 months to 12 years were studied. Clinical details, anthropometry, and details of family history of diabetes were elicited. All of them were tested for the presence of anti-GAD(65) antibodies and for pancreatic beta-cell reserve by measuring serum C-peptide response (radioimmunoassay procedures). RESULTS: All children showed a response to ODAs, had good beta-cell reserve (>/=0.6 pmol/ml on stimulation), and negligible GAD(65) antibodies indicating the presence of type 2 diabetes. The children were nonketotic; nine were obese, four had acanthosis nigricans, and one had polycystic ovary syndrome. Positive family history of diabetes was present in all cases. CONCLUSIONS: The clinical, immunological, and biochemical profile showed that the children had type 2 diabetes. The profile of type 2 diabetes was similar to that described in children in many other countries. Although less common than type 1 diabetes, type 2 diabetes in children is a condition that needs to be recognized and looked for in Asian-Indians.
Adolescent↗
Cutoff values for normal anthropometric variables in asian Indian adults.
OBJECTIVE: Asian Indians have a high risk of developing glucose intolerance with small increments in their BMI. They generally have high upper-body adiposity, despite having a lean BMI. Therefore, this analysis was performed to find out the normal cutoff values for BMI and upper-body adiposity (waist circumference [WC] or waist-to-hip ratio [WHR]) by computing their risk associations with diabetes. RESEARCH DESIGN AND METHODS: The risk of diabetes with stratified BMI, WC, or WHR was computed in 10,025 adults aged > or =20 years without a history of diabetes, and they were tested by oral glucose tolerance tests, using World Health Organization criteria. The calculations were performed separately in men and women using diabetes as the dependent variable versus normoglycemia (normal glucose tolerance) in multiple logistic regression analyses. Age-adjusted and stratified BMI, WC, or WHR were used as the independent variables, using the first stratum as the reference category. The upper limit of the stratum above which the risk association became statistically significant (P < 0.05) was considered to be the cutoff for normal values. RESULTS: Normal cutoff values for BMI was 23 kg/m(2) for both sexes. Cutoff values for WC were 85 and 80 cm for men and women, respectively; the corresponding WHRs were 0.88 and 0.81, respectively. Optimum sensitivity and specificity obtained from the receiver operator characteristic curve corresponded to these cutoff values. CONCLUSIONS: The cutoff value for normal BMI for men and women was 23 kg/m(2). The cutoff values for WC and WHR were lower in women than in men. The values were significantly lower compared with the corresponding values in white populations.
Anthropometry↗
Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians.
Haplotype combination 112/121 and its intrinsic variants (UCSNP43, -19, and -63) identified within the calpain 10 gene are associated with increased risk of type 2 diabetes in Mexican-Americans. We evaluated whether this haplotype combination and its constituent haplotypes and variants contribute to increased susceptibility to impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and type 2 diabetes in a South Indian population. Two study groups were used: 95 families ascertained through a proband with type 2 diabetes and 468 subjects recruited as part of an urban survey (69.1% with normal glucose tolerance, 12.8% with IFG/IGT, and 18.2% with type 2 diabetes). The four-locus haplotype combination 1112/1121 (UCSNP44, -43, -19, and -63) in South Indians conferred both a 10.7-fold increased risk for IFG/IGT (P = 0.001) and a 5.78- to 6.52-fold increased risk for type 2 diabetes in the two study groups (families P = 0.025, urban survey P = 0.015). A combination of the 1112 haplotype with the 1221 haplotype also appeared to increase risk for both IFG/IGT and type 2 diabetes. Contrary to what might be expected, quantitative trait analysis in the families found that transmission of the disease-related 1121 and 1112 haplotypes was associated with a reduced hip size and lower waist-to-hip ratio, respectively. This study supports the paradigm that specific haplotype combinations of calpain 10 variants increase risk of both IFG/IGT and type 2 diabetes. However, the relative infrequency of the "at-risk" combinations in the South Indian population suggests that calpain 10 is not a common determinant of susceptibility to type 2 diabetes.
Adult↗