Om P. Ganda

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS' GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF ATHEROSCLEROSIS

American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice are systematically developed statements to assist health care professionals in medical decision-making for specific clinical conditions, but are in no way a substitute for a medical professional’s independent judgment and should not be considered medical advice. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with, and not as a replacement for, their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

Somatostatinoma: a somatostatin-containing tumor of the endocrine pancreas.

We studied the pancreatic and enteric hormone profile of a 46-year-old woman who had hyperglycemia and a pancreatic tumor. Before operation, there was no evidence of overproduction of glucagon or insulin. The tumors ultrastructure had a distinctive endocrine morphology, resembling D cells. Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue). Insulin, glucagon, gastrin, vasoactive intestinal polypeptide and human pancreatic polypeptide were present in only trace quantities. The tumor cells were cultured in monolayers, which remained viable up to 51 days and released somatostatin into the culture medium. In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable. After complete resection of the tumor, our patient became euglycemic and has remained so for the past 20 months.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY - CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN - 2015

The American Association of Clinical Endocrinologists/American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. Abbreviations: A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascu...

Studies on Streptozotocin Diabetes

Both alloxan and streptozotocin produce β-cell necrosis in the rat. Previous studies have shown protection against alloxan toxicity by D-glucose, D-mannose, and the nonmetabolized analogue 3-0-methyl-D-glucose and removal of this protective effect by D-mannoheptulose. The effect of several agents (i.v. infusion) against the β-cell toxic effect of streptozotocin (60 mg./kg. i.v. in 24-hour-fasted 200-gm. male rats) was studied. Protection was determined by plasma glucose concentrations 24 and 48 hours later and, in certain experiments, by histologic examination of the islets. D-glucose and D-mannose provided no protection. Similarly, D-galactose, D-fructose, α-methyl-D-glucoside, D-L-glyceraldehyde, D-xylose, and D-glucosamine had no effect. However, 3-0-methyl-D-glucose administered immediately before streptozotocin resulted in progressive inhibition of β-cell toxicity with complete protection at 0.83 mMoles per rat. The protective effect of 3-0-methyl-D-glucose was not altered by mannoheptulose. 2-Deoxy-D-glucose, which has no effect against alloxan, provided nearly complete protection against streptozotocin at 2.2 mMoles per rat. The effects of 3-0-methyl-D-glucose and 2-deoxy-D-glucose were additive and were not altered by glucose. Furthermore, the 3-0-methyl-D-glucose as well as 2-deoxy-D-glucose protective effects were still present, albeit attenuated, when these agents were given following the administration of streptozotocin. This is in contrast to alloxan, against which 3-0-methyl-D-glucose provides protection only when given before alloxan. 3-0-Methyl-D-glucose is the only carbohydrate protective against both streptozotocin and alloxan in the rat. However, several silent differences seem to exist between the mechanisms of beta-cytotoxic effects of these two diabetogenic compounds.

Hypertension: The Major Risk Factor in Juvenile-onset Insulin-dependent Diabetics

The prevalence of hypertension in various age groups of diabetics and its role as a risk factor in juvenileonset insulin-dependent diabetics followed for 40 yr after diagnosis was evaluated. The results show clearly that hypertension is more prevalent in diabetics of any age after age 24 yr than in the general population. In this type of diabetes, although death due to renal disease occurs earlier than that due to coronary heart disease, both causes of death are significantly related to hypertension. Those patients with an onset of diabetes 13 yr of age or younger can expect to live longer following the diagnosis of diabetes mellitus than those with an onset after 13 yr of age, perhaps because hypertension appears at about the same age in both groups. Case/control analysis of the data shows that survivors have significantly less hypertension than those dying of renal or cardiac disease. Furthermore, the close temporal relationship between the onset of hypertension and the onset of proteinuria in patients with either renal or coronary deaths suggests that the hypertension in these patients is renal in origin. Two other risk factors, smoking and serum lipids, were evaluated in this population. From the data thus far accumulated, neither smoking nor lipids appear to influence mortality significantly. We conclude that hypertension is the major additive risk factor for mortality in juvenile-onset insulin-dependent diabetics.

Pre-Type I Diabetes: Linear Loss of Beta Cell Response to Intravenous Glucose

Twenty-one intravenous (i.v.) glucose tolerance tests were performed on nine subjects before the onset of overt type I diabetes mellitus. Islet cell antibodies (6 of 9 subjects) and elevated levels of la-positive T-lymphocytes (3 of 3 subjects studied) were detected during the prediabetic period. Elevations of fasting blood glucose and peak glucose during oral glucose tolerance tests were not observed until the year before onset of clinically overt diabetes. During the prediabetic period, there was a progressive loss of early-phase insulin release to i. v. glucose (rate of decline, 20–40 μU/ml insulin release/yr; correlation coefficient, 0.9).

Hyperfibrinogenemia: An important risk factor for vascular complications in diabetes

OBJECTIVE To evaluate the determinants of elevated fibrinogen levels and the impact of hyperfibrinogenemia on vascular complications in diabetes. RESEARCH DESIGN AND METHODS Plasma fibrinogen, glucose, HbA1, and lipids were measured in 116 ambulatory type I and type II diabetic patients with (n = 59) or without (n = 57) clinical evidence of micro- or macrovascular complications. In 56 of these patients, factor VII activity and CRP also were measured. Univariate and multivariate data analyses were conducted. RESULTS Overall mean ± SE fibrinogen levels in patients (339 ± 7.3 mg/dl) were elevated markedly compared with control subjects (248 ± 9.1 mg/dl). Fibrinogen levels were elevated disproportionately in patients with type II diabetes (P < 0.0001), hypertension (P = 0.0001), obesity (P < 0.0001), and vascular complications (P < 0.0001). Fibrinogen was correlated significantly with age (P < 0.001), cholesterol (P = 0.002), CRP (P < 0.001), and factor VII activity (P = 0.032), but not with plasma glucose, triglycerides, HDL cholesterol, or disease duration. Stepwise multiple regression analyses revealed that type II diabetes and presence of vascular complications were major determinants of fibrinogen. For vascular complications, fibrinogen emerged as one of only three independent predictors, the other two being diabetes duration and hypertension.

Acquired Defect in Interleukin-2 Production in Patients with Type I Diabetes Mellitus

Deficient production of interleukin-2 has been reported in Type I diabetes, but its cause has not been elucidated. We therefore measured interleukin-2 production in 27 patients with Type I diabetes, 20 patients with Type II diabetes (6 requiring insulin), 5 monozygotic twin pairs discordant for Type I diabetes, and 10 nondiabetic persons with islet-cell antibodies. Interleukin-2 production was decreased in patients with Type I diabetes as compared with controls (35.8 +/- 2.5 vs. 61.6 +/- 4.6 percent, P less than 0.001). Interleukin-2 production did not differ between patients with Type II diabetes and controls, regardless of whether the patients used insulin. Twins with Type I diabetes had decreased interleukin-2 production as compared with normal controls (33.2 +/- 5.4 vs. 61.6 +/- 4.6 percent, P less than 0.001) and with their nondiabetic twins (33.2 +/- 5.4 vs. 54.5 +/- 3.4 percent, P less than 0.005). Interleukin-2 production in nondiabetic twins and in nondiabetic persons with islet-cell antibodies was normal. There was no correlation between glycosylated hemoglobin levels and interleukin-2 production in any diabetic group. We conclude that patients with Type I diabetes have an acquired defect in interleukin-2 production, whereas patients with Type II diabetes do not, and that this defect is not correlated with an ongoing autoimmune process, with hyperglycemia, or with insulin administration or oral hypoglycemic therapy. Thus, the defect appears to be related to marked beta-cell destruction, although not to the metabolic consequences thereof or the responsible autoimmune process.

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.

Muscle nitrogen metabolism in chronic hepatic insufficiency.

Whole blood arterio-venous (A-V) differences for ammonia (NH3) and amino acids were determined across the forearm in 14 patients with decompensated alcoholic cirrhosis and hyperammonemia. NH3 was extracted by the forearm in all patients; however, the fractional extraction of NH3 was significantly less in five individuals with gross muscle wasting (13.3% versus 25.3%). There was neither a significant uptake nor release of NH3 in normal control subjects. The arterial concentrations of 12 out of 20 amino acids were strikingly diminished in the patient group. In contrast to normal subjects, in whom the release of alanine exceeds that of glutamine, the A-V difference for glutamine in the patients was threefold greater than that for alanine. The A-V differences for all other amino acids were not significantly different from zero. The results suggest that (1) muscle plays an important role in disposing of NH3 in patients with hepatic insufficiency and (2) a major fraction of NH3 taken up by muscle is released as glutamine.