Jayendra H. Shah

Intensive Glucose-Lowering Therapy Reduces Cardiovascular Disease Events in Veterans Affairs Diabetes Trial Participants With Lower Calcified Coronary Atherosclerosis

OBJECTIVE This study investigated the hypothesis that baseline calcified coronary atherosclerosis may determine cardiovascular disease events in response to intensive glycemic control within the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS At baseline, 301 type 2 diabetic participants in the VADT, a randomized trial comparing the effects of intensive versus standard glucose lowering on cardiovascular events, had baseline coronary atherosclerosis assessed by coronary artery calcium (CAC) measured by computed tomography. Participants were followed over the 7.5-year study for development of cardiovascular end points. RESULTS During a median follow-up duration of 5.2 years, 89 cardiovascular events occurred. Although intensive glucose-lowering therapy did not significantly reduce cardiovascular events in the substudy cohort as a whole, there was evidence that the response was modified by baseline CAC, as indicated by significant P values for treatment by log(CAC + 1) interaction terms in unadjusted and multivariable-adjusted models (0.01 and 0.03, respectively). Multivariable-adjusted hazard ratios (HRs) for the effect of treatment indicated a progressive diminution of benefit with increasing CAC. Subgroup analyses were also conducted for clinically relevant CAC categories: those above and below an Agatston score of 100. Among those randomized to intensive treatment, for the subgroup with CAC >100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC ≤100 had an event. The multivariable HR for intensive treatment for those with CAC >100 was 0.74 (95% CI 0.46–1.20; P = 0.21), while for the subgroup with CAC ≤100, the corresponding HR was 0.08 (0.008–0.77; P = 0.03), with event rates of 39 and 4 per 1,000 person-years, respectively. CONCLUSIONS These data indicate that intensive glucose lowering reduces cardiovascular events in those with less extensive calcified coronary atherosclerosis.

Factors affecting diabetes knowledge in Type 2 diabetic veterans

Aims/hypothesisTo describe the clinical, psychological and social factors affecting diabetes knowledge of veterans with established Type 2 diabetes.MethodsWe conducted an observational study of 284 insulin-treated veterans with stable Type 2 diabetes. All subjects completed the University of Michigan Diabetes Research and Training Centre Knowledge Test, the Diabetes Care Profile, the Mini-Mental State Examination, the Geriatric Depression Scale, and the Diabetes Family Behaviour Checklist. Stepwise multiple linear regression was used to develop a model for the diabetes knowledge score based upon clinical and psychosocial variables.ResultsOne hundred eighty subjects were evaluated in a derivation set. The mean age ± SD was 65.4±9.6 years, 94% were men, and 36% were members of a minority group. Performance on the diabetes knowledge test was poor (64.9±15.3% correct). Self-perceived understanding of all management objectives explained only 6% of the variance in the knowledge scores. Multivariate analysis showed that age, years of schooling, duration of treatment, cognitive function, sex, and level of depression were independent determinants of the knowledge score. When the model was applied to 104 subjects in a validation set, there was a strong correlation between observed and predicted scores (r=0.537; p<0.001).Conclusions/interpretationStable, insulin-treated veterans have major deficiencies in diabetes knowledge that could impair their ability to provide self-care. A multivariate model comprised of demographic variables and psychosocial profiling can identify patients who have limited diabetes knowledge and be used to assess individual barriers to ongoing diabetes education.

Verapamil-Induced Hyperprolactinemia and Galactorrhea

Excerpt Verapamil, a synthetic papaverine derivative, has been reported to have antiarrhythmic, antianginal, and antihypertensive properties in man (1). Although verapamil was introduced in Germany...

Letter: Acute hyperphosphatemia and acute persistent renal insufficiency induced by oral phosphate therapy.

Excerpt Intravenous phosphate therapy alone or combined with oral phosphate therapy on occasion has caused metastatic calcification and renal impairment (1). This report documents a case in which o...

Racial and ethnic disparities in the control of cardiovascular disease risk factors in Southwest American veterans with type 2 diabetes: the Diabetes Outcomes in Veterans Study

BackgroundRacial/ethnic disparities in cardiovascular disease complications have been observed in diabetic patients. We examined the association between race/ethnicity and cardiovascular disease risk factor control in a large cohort of insulin-treated veterans with type 2 diabetes.MethodsWe conducted a cross-sectional observational study at 3 Veterans Affairs Medical Centers in the American Southwest. Using electronic pharmacy databases, we randomly selected 338 veterans with insulin-treated type 2 diabetes. We collected medical record and patient survey data on diabetes control and management, cardiovascular disease risk factors, comorbidity, demographics, socioeconomic factors, psychological status, and health behaviors. We used analysis of variance and multivariate linear regression to determine the effect of race/ethnicity on glycemic control, insulin treatment intensity, lipid levels, and blood pressure control.ResultsThe study cohort was comprised of 72 (21.3%) Hispanic subjects (H), 35 (10.4%) African Americans (AA), and 226 (67%) non-Hispanic whites (NHW). The mean (SD) hemoglobin A1c differed significantly by race/ethnicity: NHW 7.86 (1.4)%, H 8.16 (1.6)%, AA 8.84 (2.9)%, p = 0.05. The multivariate-adjusted A1c was significantly higher for AA (+0.93%, p = 0.002) compared to NHW. Insulin doses (unit/day) also differed significantly: NHW 70.6 (48.8), H 58.4 (32.6), and AA 53.1 (36.2), p < 0.01. Multivariate-adjusted insulin doses were significantly lower for AA (-17.8 units/day, p = 0.01) and H (-10.5 units/day, p = 0.04) compared to NHW. Decrements in insulin doses were even greater among minority patients with poorly controlled diabetes (A1c ≥ 8%). The disparities in glycemic control and insulin treatment intensity could not be explained by differences in age, body mass index, oral hypoglycemic medications, socioeconomic barriers, attitudes about diabetes care, diabetes knowledge, depression, cognitive dysfunction, or social support. We found no significant racial/ethnic differences in lipid or blood pressure control.ConclusionIn our cohort, insulin-treated minority veterans, particularly AA, had poorer glycemic control and received lower doses of insulin than NHW. However, we found no differences for control of other cardiovascular disease risk factors. The diabetes treatment disparity could be due to provider behaviors and/or patient behaviors or preferences. Further research with larger sample sizes and more geographically diverse populations are needed to confirm our findings.

Calcinosis and Metastatic Calcification due to Vitamin D Intoxication

Vitamin D, a fat-soluble vitamin, can be associated with significant morbidity when prescribed in large doses. We describe a hypoparathyroid patient with vitamin D intoxication who developed painful periarticular calcinosis, nephrocalcinosis with hypertension and chronic renal failure in addition to band keratopathy and hearing loss. He was treated with combination therapy including prednisone, phosphate-binding antacid, phenytoin and disodium etidronate. After 20 months of follow-up there was a significant reduction of periarticular calcinosis, but no improvement in renal function, band keratopathy or hearing loss and possible calcification of the ossicles. The clinicopathologic features of metastatic calcification and the various treatment modalities are reviewed.

Insulin Metabolism in Hypothyroidism

Insulin resistance has been invoked to explain the glucose intolerance observed in hypothyroid patients. This possibility was studied by determining fractional and metabolic clearances of intravenously administered porcine crystalline insulin (0.1 U./kg.) and its effect on plasma glucose concentration in ten hypothyroid patients, ten normal subjects, and six treated euthyroid patients. Following administration of porcine insulin, serum immunoreactive insulin concentrations during the period of observation were similar in hypothyroid patients, in normal control subjects, and in treated euthyroid patients. Similarly, no significant differences in the mean half-life, distribution space, or fractional and metabolic clearances of insulin were observed among any of the three groups. In response to insulin administration, plasma glucose concentrations declined to the nadir of 36 ± 4, 43 ± 3, and 38 ± 4 mg. per 100 ml. in hypothyroid patients, normal control subjects, and treated euthyroid patients, respectively. Thereafter, plasma glucose steadily increased and approached the baseline value at ninety minutes in normal subjects and treated euthyroid patients. In contrast, the plasma glucose values remained significantly lower than the baseline for the rest of the procedure in hypothyroid patients. The present study demonstrates that there is no evidence of resistance to the action of insulin in hypothyroid patients. The observation of prolonged hypoglycemic action of exogenously administered insulin in hypothyroid patients might in fact suggest increased sensitivity to insulin action. These findings indicate that glucose intolerance of the hypothyroid state is not characterized by insulin resistance.

Sources of glucose variability in insulin-treated type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES).

objective  Glucose variability can be a significant barrier to glycaemic control for diabetic patients on insulin. The study identified clinical and behavioural factors associated with glucose variability in type 2 diabetes.

Glycemic Index and Insulin Response to a Liquid Nutritional Formula Compared with a Standard Meal

OBJECTIVE To determine the glycemic index and metabolic responses to a nutritional formula, and to compare these responses to those following an oral glucose meal and a standard test meal. METHODS Six male and six female healthy non-diabetic volunteers aged 18 to 48 years met screening examination and laboratory assessment criteria. Three test meals were administered, each containing 50 g of carbohydrate: nutritional formula (NF), standard test meal (ST) and a glucose test meal (GT). Each subject underwent the three test meals on separate days in randomized sequence. Blood samples were taken at intervals over 5 hours for determination of glucose, insulin and triglycerides. RESULTS The glycemic index was similar for the NF (60.8 +/- 13.1) and for the ST (57.8 +/- 12.9) meals. The incremental area under the curve for glucose was similar for NF and ST, but each was significantly lower than for the GT meal. The total area under the curve for insulin was significantly greater for the NF meal than for the ST meal. The serum triglyceride responses were similar for NF and ST meals. CONCLUSION In healthy non-diabetic subjects, the blood glucose and triglyceride responses are similar for a nutritional formula compared to an isoenergetic standard test meal. However, the insulin response differs. This information is important in managing tube-fed patients.

Effect of Ethanol on Stimulus-induced Insulin Secretion and Glucose Tolerance: A Study of Mechanisms

The effect of ethanol on stimulus-induced insulin secretion was studied, and possible mechanisms were examined in fasting unanes-thetized and unrestrained rats with indwelling jugular and aortic catheters. Glucose (150 mg.) or tolbutamide (10 mg.) was given rapidly, i.v., one hour after a gavage of ethanol or saline (control). Acutely, ethanol treatment caused marked inhibition of glucose-induced insulin secretion and impaired glucose disappearance rate. Tolbutamide-induced insulin secretion was also significantly inhibited, and decline in glucose was significantly less in ethanol-treated rats. In response to ethanol, serum calcium concentration significantly declined for two hours. In another study, an ethanol metabolite, acetate (0.4 μmole/min.) or vehicle (control) was infused for 60 minutes prior to 150 mg. glucose pulse. Acetate priming significantly potentiated glucose-induced insulin secretion and also improved glucose tolerance. It is proposed that (1) ethanol in vivo acutely induces hypocalcamie, which inhibits glucose- and tolbutamide-induced insulin secretion—which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycamie. (2) Acetate might be the actual potentiating influence on glucose-induced insulin secretion observed several hours after ethanol treatment.