Annaswamy Raji

Prevalence of diabetes, metabolic syndrome, and cardiovascular risk factors in US Asian Indians: results from a national study

BACKGROUND Although studies of immigrant Asian Indians in other countries show high rates of diabetes (DM), metabolic syndrome (MetS), and cardiovascular disease (CVD), no randomized, population-based studies of this rapidly growing ethnic group exist in the US. METHODS The sample comprised 1038 randomly selected Asian Indian immigrants, aged 18 years and older at seven US sites. Prevalence of diabetes and MetS (age-adjusted and sex-adjusted means) was estimated and ANOVA was used to calculate gender and group differences (normoglycemia/impaired fasting glucose/diabetes) for CVD risk factors. RESULTS The mean age was 48.2 years. The majority of respondents were male, married, educated, and with some form of health insurance. Prevalence of diabetes was 17.4%, and 33% of the respondents had prediabetes. Cardiovascular risk factors, especially high levels of triglycerides, total cholesterol, LDL cholesterol, homocysteine, and C-reactive protein, and low levels of HDL cholesterol, were also prevalent; elevated lipoprotein(a) was not observed. The age-adjusted prevalence of MetS was 26.9% by the original NCEP/ATP III criteria, 32.7% by the modified NCEP/ATP III criteria, and 38.2% by the IDF criteria. The MetS rates for women, but not for men, increased with age using all three criteria. There was a progressive worsening of all metabolic parameters as individuals progressed from normal to IFG to diabetes. CONCLUSION The prevalence rates of diabetes and MetS among US Asian Indians are higher than reported in earlier, nonrandomized, smaller surveys. These data provide a firm basis for future mechanistic and interventional studies.

Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia

Screening for primary hyperaldosteronism (PHA) is often indicated in individuals with resistant hypertension or hypokalaemia. However, in the far larger subset of the hypertensive population who do not fit into these criteria, the evidence for screening is conflicting and dependent on the disease prevalence. The purpose of this study was to examine the prevalence of PHA in a large population with mild to moderate hypertension and without hypokalaemia using a carefully controlled study protocol including a normotensive control population. Hypertensive subjects underwent medication washout and both hypertensive and normotensive subjects placed on a high-sodium diet prior to biochemical and haemodynamic testing. Study specific cutoff values were based on results from the normotensive population studied under identical conditions. A screening test (serum aldosterone/PRA ratio [ARR]>25 with a serum aldosterone level >8 ng/dl) was followed by a confirmatory test (urine aldosterone excretion rate [AER] >17 μg/24 h) to demonstrate evidence of PHA. An elevated ARR with a concomitant elevated serum aldosterone was present in 26 (7.5%) individuals. Of these, 11 (3.2%) had an elevated AER, consistent with evidence of PHA. Individuals with PHA had higher blood pressure and lower serum potassium levels while on a high-sodium diet. Sodium restriction neutralized these differences between PHA and essential hypertensives. The prevalence of PHA in this mild to moderate hypertensive population without hypokalaemia is at most 3.2%, a rate that might lead to excessive false positives with random screening in comparable populations. Hyperaldosteronism, when present, is responsive to sodium restriction.

Insulin resistance in hypertensives: effect of salt sensitivity, renin status and sodium intake.

Objective Homeostasis Model Assessment (HOMA index) is predictive of insulin sensitivity in normal and diabetic patients. This study was designed to see if insulin resistance in hypertensives, measured using the HOMA index, differs, based on salt sensitivity, renin status and sodium intake. Methods Fasting insulin and glucose were determined in subsets of 426 essential hypertensives, and normotensives. HOMA was calculated as fasting glucose (mmol) × fasting insulin (μU/ml)/22.5. Results Four hundred and twenty-six essential hypertensives and normotensives from four HERMES centers form the basis of this report. There was no difference in the HOMA index between hypertensives and normotensives (P = 0.291) or between hypertensives grouped according to blood pressure salt sensitivity (P = 0.153). However, when essential hypertensives were subgrouped by renin status, the low-renin group had significantly lower (P < 0.01) HOMA index than the normal/high-renin group. When normal/high-renin group was divided into modulators and non-modulators, the non-modulators had significantly higher HOMA index (P < 0.001) than other hypertensive subsets. The effect of sodium intake on the HOMA index was significant only for non-modulators (P < 0.002), with salt restriction increasing insulin resistance. Conclusion Insulin sensitivity differs among subsets of essential hypertension, non-modulators being most insulin resistant and the low-renin subset insulin sensitive. Salt restriction might have an adverse effect on insulin sensitivity in non-modulators. The reduction in cardiovascular risk seen in low-renin hypertensives may be related to their increased insulin sensitivity; in contrast, the clustering of cardiovascular risk factors seen in non-modulators may be due to increased insulin resistance.

Cross-sectional Associations between Abdominal and Thoracic Adipose Tissue Compartments and Adiponectin and Resistin in the Framingham Heart Study

OBJECTIVE To test the association of regional fat depots with circulating adiponectin and resistin concentrations and to assess the potential mediating effect of adipokines on associations between abdominal fat depots and cardiometabolic risk factors. RESEARCH DESIGN AND METHODS Participants from the Framingham Heart Study offspring cohort (n = 916, 55% women; mean age 59 years) free of cardiovascular disease underwent computed tomography measurement of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), pericardial fat, and intrathoracic fat volumes and assays of circulating adiponectin and resistin. RESULTS VAT, SAT, pericardial fat, and intrathoracic fat were negatively correlated with adiponectin (r = −0.19 to −0.34, P < 0.001 [women]; r = −0.15 to −0.26, P < 0.01 [men] except SAT) and positively correlated with resistin (r = 0.16–0.21, P < 0.001 [women]; r = 0.11–0.14, P < 0.05 [men] except VAT). VAT increased the multivariable model R2 for adiponectin from 2–4% to 10–13% and for resistin from 3–4% to 3–6%. Adjustment for adipokines did not fully attenuate associations between VAT, SAT, and cardiometabolic risk factors. CONCLUSIONS Adiponectin and resistin are correlated with fat depots cross-sectionally, but none of the adipokines can serve as surrogates for the fat depots. Relations between VAT, SAT, and cardiometabolic risk factors were not fully explained by adiponectin or resistin concentrations.

Regional Brain Activation during Hypoglycemia in Type 1 Diabetes

CONTEXT Mechanisms underlying the brain response to hypoglycemia are not well understood. OBJECTIVE Our objective was to determine the blood glucose level at which the hypothalamus and other brain regions are activated in response to hypoglycemia in type 1 diabetic patients and control subjects. DESIGN This was a cross-sectional study evaluating brain activity using functional magnetic resonance imaging in conjunction with a hyperinsulinemic hypoglycemic clamp to lower glucose from euglycemia (90 mg/dl) to hypoglycemia (50 mg/dl). SETTING The study was performed at the Brain Imaging Center in the McLean Hospital. STUDY PARTICIPANTS Seven type 1 diabetic patients between 18 and 50 yr old and six matched control subjects were included in the study. INTERVENTION Hyperinsulinemic hypoglycemic clamp was performed. MAIN OUTCOME MEASURES Blood glucose level at peak hypothalamic activation, amount of regional brain activity during hypoglycemia in both groups, and difference in regional brain activation between groups were calculated. RESULTS The hypothalamic region activates at 68 +/- 9 mg/dl in control subjects and 76 +/- 8 mg/dl in diabetic patients during hypoglycemia induction. Brainstem, anterior cingulate cortex, uncus, and putamen were activated in both groups (P < 0.001). Each group also activated unique brain areas not active in the other group. CONCLUSIONS This application of functional magnetic resonance imaging can be used to identify the glucose level at which the hypothalamus is triggered in response to hypoglycemia and whether this threshold differs across patient populations. This study suggests that a core network of brain regions is recruited during hypoglycemia in both diabetic patients and control subjects.

Peroxisome proliferator activated receptor gamma and its activation in the treatment of insulin resistance and atherosclerosis: issues and opportunities.

Atherosclerosis remains a major complication of type 2 diabetes mellitus. Increasing data suggest insulin resistance, and its associated metabolic abnormalities, may underlie many of the cardiovascular complications seen among patients with insulin resistance and/or diabetes mellitus. This insight has also suggested that therapeutic approaches targeting insulin resistance may not only improve metabolism but also limit complications like atherosclerosis and the inflammation that contributes to it. Thiazolidinediones, agonists of the nuclear receptor peroxisome proliferator activated receptor gamma, are one such insulin-sensitizing therapeutic intervention in current use among patients with type 2 diabetes mellitus. The existing data regarding thiazolidinedione effects on the cardiovascular system are reviewed and considered, along with the future prospects for this emerging drug class.

Comparison of Insulin Sensitivity Measures in South Asians

OBJECTIVE South Asians have increased visceral adiposity, insulin resistance and greater prevalence of type 2 diabetes and cardiovascular disease when compared to Caucasians of European origin. Surrogate markers of insulin resistance such as the composite insulin sensitivity (Matsuda) index correlate with glucose clamps in other populations, but ethnicity can affect these indices. We compared the Matsuda index, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglyceride/HDL ratio to insulin sensitivity derived from euglycemic clamps in healthy South Asians and Caucasians. MATERIALS/METHODS Twenty-three healthy South Asians and 18 Caucasians matched for age (mean±SE=33.6±2.1 vs. 36.0±3.0 years) and BMI (25.2±1.1 vs. 24.6±0.9 kg/m(2)) underwent 75 g oral glucose tolerance test (OGTT), 2-h euglycemic hyperinsulinemic clamp (240 pmol·m(-2)·min(-1)), fasting lipid profile, and anthropometric measures. RESULTS South Asians had higher fasting insulin (41±5 vs. 21±2 pmol/l; p=0.002) and lower HDL-C (1.25±0.06 vs. 1.56±0.10 mmol/l; p=0.010), but similar fasting glucose (5.0±0.1 vs. 4.9±0.1 mmol/l) levels vs. Caucasians. South Asians had significantly decreased measures of insulin sensitivity derived from both the euglycemic clamp (24.9±1.3 vs. 41.4±1.9 μmol·kg(-1)·min(-1); p<0.0001) and OGTT (Matsuda Index 7.60±0.99 vs. 13.60±1.79; p=0.004). The Matsuda index correlated highly with clamp insulin sensitivity in South Asians (r=0.50; p=0.014) and Caucasians (r=0.47; p=0.046). HOMA-IR, QUICKI, and triglyceride/HDL ratio correlated with clamp values in South Asians, but not in Caucasians. CONCLUSIONS In South Asians, Matsuda index, HOMA-IR, QUICKI, and triglyceride/HDL ratio offer simple and valid surrogate measures of insulin sensitivity that can be employed in larger clinical or epidemiological studies in this ethnic group.

Familial Aggregation of Insulin Resistance and Cardiovascular Risk Factors in Hypertension

The authors assessed the familial aggregation of cardiometabolic abnormalities (elevated homeostasis model assessment [HOMA], triglycerides [TG], and low‐density lipoprotein [LDL] and reduced high‐density lipoprotein [HDL]) among hypertensive siblings (N=287 from 138 families). Evidence for familial aggregation required sibling‐pair concordance of outcome variables dichotomized according to predefined values (concordance for highest‐quartile HOMA [>3.3], TG [>170 mg/dL], and LDL [>138 mg/dL] and lowest‐quartile HOMA for HDL [<32 mg/dL]). Hypertensive individuals with insulin resistance (high‐quartile HOMA) had higher TG and lower HDL and LDL levels compared with insulinsensitive hypertensives. High‐quartile HOMA, TG, and LDL aggregated in hypertensive families, and TG plus HOMA coaggregated. HDL did not show aggregation. In a multivariate logistic regression, the only significant predictor of an individuals HOMA status was a siblings HOMA status in a model including age, sex race, and body mass index (odds ratio=9.12; 95% confidence interval, 3.64–23.14; P<.001). Cardiometabolic variables demonstrate heritability in hypertensive families. Further exploration of common genetic susceptibility loci in hypertension involving these factors is warranted.