Pheochromocytoma: a review.

Pheochromocytomas are catecholamine producing neuroendocrine tumors that can be adrenal or extra-adrenal in origin. The classic symptoms of pheochromocytoma are headache, palpitation, anxiety and diaphoresis and the tumor can occur at any age with equal gender distribution. In patients with an established mutation or hereditary syndrome the condition may manifest at a younger age than in those with sporadic disease. Pheochromocytoma can be associated with certain genetic syndromes such as multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis (NF) and von Hippel-Lindau (VHL) syndrome. Pheochromocytoma is diagnosed with biochemical confirmation of hormonal excess followed by anatomical localization (CT or MRI). The mainstay of definitive therapy is surgical resection. In this review, we discuss in detail about the symptomatology, diagnosis, genetic aspects and management of pheochromocytoma.

Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial.

AIMS: This study examined the effects of pioglitazone on body weight and bone mineral density (BMD) prospectively in patients with impaired glucose tolerance as pioglitazone (TZD) increases body weight and body fat in diabetic patients and increases the risk of bone fractures. METHODS: A total of 71 men and 163 women aged 49.3 (10.7) years [mean (s.d.)]; body mass index (BMI), 34.5 (5.9) kg/m(2) were recruited at five sites for measurements of body composition by dual energy X-ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted. RESULTS: Mean follow-up was 33.6 months in the pioglitazone group and 32.1 months in the placebo group. Body weight increased 4.63 ± 0.60 (m ± s.e.) kg in the pioglitazone group compared to 0.98 ± 0.62 kg in the PIO group (p < 0.0001). Body fat rose 4.89 ± 0.42 kg in the pioglitazone group compared to 1.41 ± 0.44 kg, (p < 0.0001) in placebo-treated subjects. The increase in fat was greater in legs and trunk than in the arms. BMD was higher in all regions in men and significantly so in most. PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men. Bone mineral content also decreased significantly in arms, legs, trunk and in the total body. CONCLUSIONS: Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in several regions of the body.

Safety and tolerability of vildagliptin vs. thiazolidinedione as add-on to metformin in type 2 diabetic patients with and without mild renal impairment: a retrospective analysis of the GALIANT study.

OBJECTIVE: This retrospective analysis assessed safety and tolerability of vildagliptin (Vilda) as an add-on to metformin in type 2 diabetes mellitus (T2DM) patients with normal renal function (GFR >80mL/min/1.73m(2)) and mild renal impairment (GFR: >50 to ≤80mL/min/1.73m(2)). METHODS: Adverse events (AE) from this 12-week, randomized, open-label study comparing Vilda 100mg and thiazolidinediones (TZD) as an add-on therapy in patients with T2DM inadequately controlled (HbA(1c): 7-10%) on a stable dose of metformin (≥1000mg/day) were analyzed. RESULTS: Of 2627 randomized patients, 1278 in the Vilda and 635 in the TZD groups had normal renal function; 463 in the Vilda and 230 in the TZD groups had mild renal impairment. Higher incidence of headache and rash was noted in both Vilda groups, whereas those with mild renal impairment receiving TZD experienced a higher incidence of peripheral edema and URI. Fewer patients in the Vilda group discontinued the study due to AEs compared to TZD group. Serious AEs were greater in TZD groups (normal: 2.4%; mild renal impairment: 3.0%) compared to Vilda groups (normal: 1.6%; mild renal impairment: 2.4%). CONCLUSION: The safety profile of Vilda or TZD as an add-on to metformin was similar in patients with mild renal impairment and normal renal function.

Determinants of glucose tolerance in impaired glucose tolerance at baseline in the Actos Now for Prevention of Diabetes (ACT NOW) study.

AIMS/HYPOTHESIS: The aim of the study was to examine the determinants of oral glucose tolerance in 602 persons with impaired glucose tolerance (IGT) who participated in the Actos Now for Prevention of Diabetes (ACT NOW) study. METHODS: In addition to the 602 IGT participants, 115 persons with normal glucose tolerance (NGT) and 50 with impaired fasting glucose (IFG) were identified during screening and included in this analysis. Insulin secretion and insulin sensitivity indices were derived from plasma glucose and insulin during an OGTT. The acute insulin response (AIR) (0-10 min) and insulin sensitivity (S(I)) were measured with the frequently sampled intravenous glucose tolerance test (FSIVGTT) in a subset of participants. RESULTS: At baseline, fasting plasma glucose, 2 h postprandial glucose (OGTT) and HbA(1c) were 5.8 +/- 0.02 mmol/l, 10.5 +/- 0.05 mmol/l and 5.5 +/- 0.04%, respectively, in participants with IGT. Participants with IGT were characterised by defects in early (DeltaI (0-30)/DeltaG (0-30) x Matsuda index, where DeltaI is change in insulin in the first 30 min and DeltaG is change in glucose in the first 30 min) and total (DeltaI(0-120)/DeltaG(0-120) x Matsuda index) insulin secretion and in insulin sensitivity (Matsuda index and S(I)). Participants with IGT in whom 2 h plasma glucose was 7.8-8.3 mmol/l had a 63% decrease in the insulin secretion/insulin resistance (disposition) index vs participants with NGT and this defect worsened progressively as 2 h plasma glucose rose to 8.9-9.94 mmol/l (by 73%) and 10.0-11.05 mmol/l (by 80%). The Matsuda insulin sensitivity index was reduced by 40% in IGT compared with NGT (p < 0.005). In multivariate analysis, beta cell function was the primary determinant of glucose AUC during OGTT, explaining 62% of the variance. CONCLUSION: Our results strongly suggest that progressive beta cell failure is the main determinant of progression of NGT to IGT.

Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial--a primary care, type 2 diabetes study.

AIM: To assess the efficacy and tolerability of vildagliptin compared with thiazolidinediones (TZDs) as an add on to metformin treatment in a primary care patient population with type 2 diabetes. METHODS: This was a randomized, 12-week, open-label study comparing vildagliptin (100 mg, n = 1653) and TZD (agent and dose at the investigators' discretion, n = 825) add-on therapy in patients inadequately controlled [haemoglobin A(1C) (HbA(1c)): 7-10%] on a stable dose of metformin (> or =1000 mg/day). The primary objective was to test non-inferiority of vildagliptin to TZDs for the difference in change in HbA(1c) from baseline [established if the upper limit of the two-sided 95% confidence intervals (CI) did not exceed 0.4%]. RESULTS: Mean (+/- s.e.) change in HbA(1c) from baseline to study endpoint was -0.68 +/- 0.02% in the vildagliptin group and -0.57 +/- 0.03% in the TZD group. The difference between groups was -0.11% (95% CI: -0.17% and -0.04%), establishing the non-inferiority of vildagliptin (p = 0.001) after 3 months of treatment. Vildagliptin was non-inferior to TZDs for subgroups of race, age and body mass index. Body weight increased in the TZD group (0.33 +/- 0.11 kg) and decreased in the vildagliptin group (mean: -0.58 +/- 0.09 kg; p < 0.001 for difference). Adverse events occurred in similar proportions of patients in both groups (vildagliptin: 39.5% and TZD: 36.3%) Hypoglycaemia and abnormal changes in liver enzymes were uncommon. CONCLUSIONS: This short-term study suggests that vildagliptin is as effective as TZDs after 3-month treatment as an add-on to metformin in a primary care population that included diverse patient subgroups.

Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea.

AIM: To compare the efficacy and tolerability of vildagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled [haemoglobin A(1c) (HbA(1c)) 7.5 to 11%] with prior sulphonylurea (SU) monotherapy. METHODS: This 24-week, multicentre, randomized, double-blind, placebo-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (50 mg given once or twice daily) vs. placebo added to glimepiride (4 mg once daily) in 515 patients with T2DM. Adjusted mean changes from baseline to end-point (AMDelta) in HbA(1c), fasting plasma glucose, fasting lipids and body weight were compared by analysis of covariance. RESULTS: The between-group difference (vildagliptin - placebo) in AMDelta HbA(1c) was -0.6 +/- 0.1% in patients receiving vildagliptin 50 mg daily and -0.7 +/- 0.1% in those receiving 100 mg daily (p < 0.001 vs. placebo for both). Greater efficacy was seen in patients > or =65 years of age (-0.7 +/- 0.1% and -0.8 +/- 0.2% for 50 and 100 mg daily respectively) and in patients with baseline HbA(1c) > 9% (Delta = -1.0 +/- 0.2% and -0.9 +/- 0.2% for 50 and 100 mg daily respectively). Relative to placebo, patients receiving vildagliptin also had improvements in beta-cell function and postprandial glucose, with small changes in fasting lipids and body weight. The incidences of adverse events (AEs) (67.1, 66.3 and 64.2%) and serious AEs (2.9, 2.4 and 5.1%) were similar in patients receiving 50 mg vildagliptin, 100 mg vildagliptin or placebo respectively. The incidence of hypoglycaemic events was low but slightly higher in the group receiving vildagliptin 100 mg (3.6%) than in the group receiving vildagliptin 50 mg (1.2%) or placebo (0.6%). CONCLUSIONS: In patients with T2DM inadequately controlled with prior SU monotherapy, addition of vildagliptin (50 or 100 mg daily) to glimepiride (4 mg once daily) improves glycaemic control and is well tolerated. Addition of vildagliptin 50 mg daily to SU monotherapy may be a particularly attractive therapy in elderly patients.

Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database.

AIM: To assess the effects of 24-week treatment with vildagliptin on measures of beta-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). METHODS: Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of beta-cell function [homeostasis model assessment of beta-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test-derived) measures of beta-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). RESULTS: In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AMDelta) = 10.3 +/- 1.5] and vs. placebo (between-treatment difference in AMDelta = 11.5 +/- 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AMDelta = -0.05 +/- 0.01) and vs. placebo (between-treatment difference in AMDelta = -0.09 +/- 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test-derived parameters, and ISR/G (between-treatment difference in AMDelta = 9.8 +/- 2.8 pmol/min/m(2)/mM, p < 0.001) and the insulinogenic index(0-peak glucose) (between-treatment difference in AMDelta = 0.24 +/- 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. CONCLUSIONS: Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test-derived measures of beta-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov.

The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results.

OBJECTIVE: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. METHODS: Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim. RESULTS: Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI. CONCLUSIONS: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).

Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer.

Tamoxifen is a nonsteroidal anti-estrogenic drug used for adjuvant treatment of breast cancer and recently as a chemopreventative agent for breast cancer and, on an investigational basis, for other cancers. To date there are case reports of hypertriglyceridemia and fatty liver disease in tamoxifen users. Fatty liver is associated with visceral obesity and other components of the metabolic syndrome. Here we evaluated steatosis and adipose tissue distribution by CT scan in a cross-sectional study of 32 women on tamoxifen and 39 control women. Tamoxifen users had more visceral adipose tissue (VAT) and more liver fat than controls. This is the first study to demonstrate that fatty liver and intra-abdominal fat accumulation are common in breast cancer patients receiving tamoxifen. Prospective studies of tamoxifen should monitor metabolic changes in obese women with or without breast cancer.

C-peptide and glucagon profiles in minority children with type 2 diabetes mellitus.

The present study was conducted to determine the extent of insulin deficiency and glucagon excess in the hyperglycemia of type 2 diabetes in children. The incidence of type 2 diabetes mellitus in children and adolescents has increased substantially over the past several years. Because insulin and glucagon action both regulate blood glucose concentration, we studied their responses to mixed meals in children with type 2 diabetes. Subjects were 24 patients with type 2 diabetes compared with 24 controls, aged 9--20 yr (predominantly African-Americans), matched for body mass index and sexual maturation. All of those with diabetes were negative for antibodies to glutamic acid decarboxylase. Plasma glucose, glucagon, and serum C-peptide concentrations were measured at 0, 30, 60, 90, and 120 min after a mixed liquid meal (Sustacal) ingestion (7 mL/kg body weight; maximum, 360 mL). The area under the curve (AUC) was calculated by trapezoidal estimation. The incremental C-peptide (Delta CP) in response to the mixed meal was calculated (peak -- fasting C-peptide). The plasma glucose AUC was significantly greater in patients than in controls (mean +/- SEM, 1231 +/- 138 vs. 591 +/- 13 mmol/L x min; P < 0.001). The Delta CP was significantly lower in those with diabetes than in controls (1168 +/- 162 vs. 1814 +/- 222 pmol/L; P < 0.02). Glucagon responses did not differ between the two groups. Hyperglycemia is known to inhibit glucagon secretion. Therefore, our patients with substantial hyperglycemia would be expected to have decreased glucagon responses compared with controls and are thus relatively hyperglucagonemic. Patients were divided into poorly and well controlled subgroups (glycosylated hemoglobin A(1c), > or =7.2% and <7.2%, respectively). There were no significant differences in the Delta CP and glucagon responses between these two subgroups. We next analyzed the data in terms of duration of diabetes (long term, > or =1 yr; short term, <1 yr). The CP was significantly lower in long- vs. short-term patients (768 +/- 232 vs. 1407 +/- 199 pmol/L; P < 0.05). The plasma glucagon AUC was significantly higher in the long- vs. short-term patients (9029 +/- 976 vs. 6074 +/- 291 ng/L x min; P < 0.001). Hemoglobin A(1c) did not differ between long- vs. short-term patients. Our results indicate that relative hypoinsulinemia and hyperglucagonemia represent the pancreatic beta- and alpha-cell dysfunctions in children with type 2 diabetes. The severity of both beta- and alpha-cell dysfunctions appears to be determined by the duration of diabetes.

Insulin resistance and its treatment by thiazolidinediones.

Insulin resistance is a change in physiologic regulation such that a fixed dose of insulin causes less of an effect on glucose metabolism than occurs in normal individuals. The normal compensatory response to insulin resistance is an increase in insulin secretion that results in hyperinsulinemia. If the hyperinsulinemia is sufficient to overcome the insulin resistance, glucose regulation remains normal; if not, type 2 diabetes ensues. Associated with insulin resistance, however, is a cluster of other metabolic abnormalities involving body fat distribution, lipid metabolism, thrombosis and fibrinolysis, blood pressure regulation, and endothelial cell function. This cluster of abnormalities is referred to as the insulin resistance syndrome or the metabolic syndrome. It is causally related not only to the development of type 2 diabetes but also to cardiovascular disease. A major unresolved issue is whether there is a single underlying cause of this syndrome and, if so, what might it be? Several promising hypotheses have been proposed. There are some data to support the hypothesis that fetal malnutrition imprints on metabolic regulatory processes that, in later adult life, predispose to the development of the insulin resistance syndrome. Visceral obesity also has been a candidate for the cause of the syndrome. Whatever mechanism is ultimately found to be responsible, it will undoubtedly have both genetic and environmental components. Among the biochemical mediators that are likely to be responsible for the interference with insulin's effects on intermediary metabolism are free fatty acids and other products from adipose tissue. Recent data suggest that the substances stimulate serine phosphorylation of molecules involved in the initial steps of insulin action, thereby blocking the ability of these molecules to be tyrosine phosphorylated and initiate the subsequent steps of the insulin action cascade. The thiazolidinediones are a new class of agents that have been developed to treat type 2 diabetic patients. These drugs act as peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. Following their binding to the receptor, the heterodimer molecule that contains the binding site is activated. The activated complex binds to the response elements of specific genes that regulate molecules that effect insulin action and lipid metabolism. These genes are either activated or inhibited. Specifically, the thiazolidinediones improve insulin action and decrease insulin resistance. The exact mechanism by which these agents decrease insulin resistance is not clear but they do decrease the elevated free fatty acid levels present in insulin-resistant patients and they appear to change the body distribution of adipose tissue. Treatment of insulin-resistant type 2 diabetic patients with thiazolidinediones not only improves glycemic control and decreases insulin resistance, it also improves many of the abnormalities that are part of the insulin resistance syndrome.

Near-normoglycaemic remission in African-Americans with Type 2 diabetes mellitus is associated with recovery of beta cell function.

AIMS: To prospectively determine the frequency of remission and possible mechanism of beta cell recovery in non-Whites with Type 2 diabetes mellitus in the setting of intensive glycaemic regulation using pharmacological agents. METHODS: Twenty-six consecutive, newly diagnosed African-American, Type 2 diabetic patients presenting primarily for severe hyperglycaemia (31.0+/-12.8 mmol/l) were followed for at least 1 year. Initial hospitalization included treatment with insulin, fluids and electrolytes. Outpatient intensive glycaemic regulation included insulin or glibenclamide, diabetes education and diet that altered nutrient content. Plasma glucose and C-peptide responses to an oral glucose tolerance test and HbA1c were measured at < 14, 15-56 and 57-112 days after presentation. Remission was defined as a HbA1c < or = 6.3% and fasting plasma glucose < 6.9 mmol/l, 3 months after discontinuing all pharmacological agents. RESULTS: Eleven of 26 patients (42.3%) developed remission after a mean of 83 days of pharmacological treatment and remained in remission during follow-up for 248-479 days; one relapsed after 294 days. Fifteen patients who did not develop a remission and were followed for 168-468 days, required continuing pharmacological therapy to be well-controlled. (mean HbA1c = 7.1%). There was no significant difference in age, sex, plasma glucose at presentation, initial glycaemic regulation, final body mass index, magnitude of weight change or pharmacological agents used for treatment between the two groups. Plasma C-peptide response to oral glucose was initially (< 14 days) suppressed in all subjects and subsequently increased. The increase was significantly greater in those who underwent a remission than those who did not. Neither significant weight loss nor severe hypoglycaemia was observed in either group during intensive treatment. CONCLUSIONS: Forty-two per cent of newly diagnosed, unselected African-Americans with Type 2 diabetes, treated intensively using pharmacological agents, education and diet developed near-normoglycaemic remission. Remission was associated with a greater recovery of glucose-stimulated insulin secretion suggesting that therapies directed at promoting beta cell recovery and preservation are potentially useful approaches to the treatment of Type 2 diabetes mellitus.

Construct validity of scores/measures from a developmental assessment in mathematics using classical and many-facet Rasch measurement.

Data from a developmental assessment comprised of 9 short answer mathematics tasks were validated using classical and three-faceted Rasch measurement methods. Field test data from a mixed age elementary school sample (N=280) were analyzed. Descriptive statistics on scores from the overall scale and two subdomains indicated improved performance with age. The data showed better fit with a two-factor model corresponding with the subdomain structure (Bentler's CFI=.94), than a one factor model (CFI=.87). The inter-factor correlation was.76. Convergent validity coefficients of scores with scaled scores of the Stanford AchievementTest mathematics battery ranged from.28 to.47; internal consistency reliability of the total and subdomain scores ranged from.87 to.89, respectively; and median inter-rater reliability was.75. On average, persons, tasks and raters showed acceptable fit with the three-facet Rasch model. Rasch logit difficulties of tasks suggested an ordered scale structure, although tasks tended to have high difficulty levels. The original and calibrated task ordering was consistent at the extreme ends of the scale. Gaps identified on the Rasch item map suggested a need for additional task construction. Conceptual and procedural differences in each technique are considered in deciding future improvements to the scale.

Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men.

There is a high prevalence of type 2 diabetes mellitus and coronary artery disease among urban and migrant Asian Indians despite the absence of traditional risk factors. Evidence exists that Asian Indians are more hyperinsulinemic than Caucasians and that hyperinsulinemia may be important in the development of these diseases. To test whether insulin action was related to total or regional adiposity and to explore the potential role of plasma leptin and lipids, we measured insulin-mediated glucose disposal by the euglycemic insulin clamp, adipose distribution and muscle volume using computed axial tomography, and fasting serum leptin and lipid levels in 20 healthy Asian Indian male volunteers (age, 36 +/- 10 yr). A mean body mass index of 24.5 +/- 2.5 kg/m2 was associated with an unusually high percentage of body fat (33 +/- 7%). The majority of the fat was sc, and 16% was visceral (intraabdominal) adipose tissue. The majority (66%) of these nonobese men were insulin resistant. The mean fasting serum leptin level was 7.6 +/- 3.3 ng/mL. Insulin action was inversely correlated with visceral adipose tissue, not total or abdominal sc adipose tissue. In contrast, leptin levels correlated with sc and total (not visceral) adipose tissue. Serum triglyceride and high density lipoprotein cholesterol levels were inversely correlated with each other and were directly related to insulin resistance and visceral (not subcutaneous) fat. Increased visceral fat in Asian Indians is associated with increased generalized obesity, which is not apparent from their nonobese body mass index. Increased visceral fat is related to dyslipidemia and increased frequency of insulin resistance and may account for the increased prevalence of diabetes mellitus and cardiovascular disease in Asian Indians.

Hyperfiltration in African-American patients with type 2 diabetes. Cross-sectional and longitudinal data.

OBJECTIVE: Hyperfiltration may play a role in the development of diabetic nephropathy. African-American patients with diabetes have more than a fourfold increase in end-stage renal disease. The purpose of this study is to evaluate the impact of hyperfiltration on renal function in African-American patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Renal function of 194 African-American patients with diagnosed type 2 diabetes from 1 month to 36 years was assessed by studies of isotopic glomerular filtration rate (GFR), serum creatinine, creatinine clearance, and 24-h urinary albumin excretion rates. Thirty-four patients with a duration of diagnosed type 2 diabetes from 1 month to 10 years were found to have hyperfiltration (GFR > or = 140 ml.min-1.1.73 m-2). Fifteen of these patients received longitudinal follow-up of renal function for as long as 15 years after the initial study. RESULTS: Hyperfiltration is present in 15 (36%) of 42 patients whose duration of diagnosed type 2 diabetes is < 1 year, and it persists for up to 10 years in 14-20% of patients with diagnosed type 2 diabetes. Patients with hyperfiltration are younger than their counterparts without hyperfiltration when matched for duration of diagnosed diabetes. When followed over time, those patients with hyperfiltration were not more likely to develop impaired renal function as measured by GFR or creatinine clearance. CONCLUSIONS: Hyperfiltration does not identify patients at risk for deterioration in renal function.

Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects.

To determine the interrelationship among insulin action, total or regional adiposity, and sex, we measured insulin-mediated glucose disposal by the euglycemic insulin clamp and adipose distribution using computed axial tomography (22 scans) in 32 black men and 20 black women with non-insulin-dependent diabetes mellitus (age 48 +/- 9 and 54 +/- 9 yr, body mass index 26.3 +/- 2.3 and 27.2 +/- 2.6 kg/m2, respectively). Women had approximately 80% more total and subcutaneous fat volume than men (31.8 +/- 8.3 vs. 18.6 +/- 6.1 and 28.5 +/- 7.3 vs. 14.7 +/- 4.6 liters) and less muscle volume (22.9 +/- 3.7 vs. 35.1 +/- 3.8 liters). Visceral fat volume did not differ between men and women (3.49 +/- 1.65 vs. 2.96 +/- 1.22 liters). Despite these body composition differences, an inverse nonlinear relationship existed between glucose disposal and visceral fat independent of sex (r = -0.58, P < 0.0001; men r = -0.60 and women r = -0.59; the slope and intercept were not different in men and women). Visceral fat explained a significant portion (34%) of variance in insulin-mediated glucose disposal, whereas total or subcutaneous fat and sex did not. Visceral fat appears to affect glucose disposal over a restricted range (up to approximately 2.5 l/m2 body surface area.

Utility of untimed urinary albumin measurements in assessing albuminuria in black NIDDM subjects.

OBJECTIVE: To determine the usefulness of an untimed morning urine specimen in screening a black NIDDM population attending an urban diabetes clinic for microalbuminuria. RESEARCH DESIGN AND METHODS: Untimed morning specimens were provided by 218 black NIDDM subjects. Of the 218 subjects, 123 also provided 24-h urine specimens. The 24-h specimens were assayed for albumin excretion rate (AER) in milligrams per 24 h, and the albumin-to-creatinine ratio (A-to-C) in micrograms per milligram was determined on the untimed morning urine specimen. RESULTS: Correlation between the A-to-C ratio and the 24-h AER was 0.96 (P = 0.0001). In the range of clinical proteinuria, r was 0.92 (P = 0.003, n = 7). In the range of microalbuminuria, r was 0.55 (P = 0.005, n = 26), and in the normal range, r was 0.59 (P < or = 0.0001, n = 90). Analysis of the untimed urine specimens from 218 black NIDDM subjects showed that 171 had A-to-C < 30 micrograms/mg, 38 had A-to-C 30-300 micrograms/mg, and 9 had A-to-C > 300 micrograms/mg. Data were grouped according to duration of NIDDM and the presence or absence of hypertension. None of the newly diagnosed NIDDM patients (< 1 year) (n = 40) had microalbuminuria. The frequency of microalbuminuria and clinical proteinuria increased with 1) duration of NIDDM 5-10 years (odds ratio [OR], 3.39; 95% CI 1.17-9.82),2) duration of NIDDM > 10 years (OR, 11.03; 95% CI 4.16-29.25), and 3) presence of hypertension (OR, 2.59; 95% CI I.20-5.61). CONCLUSIONS: The A-to-C ratio obtained from an untimed morning urine specimen correlates with the AER from a 24-h collection. In black subjects with newly diagnosed NIDDM, microalbuminuria is not present to a significant degree. Duration of NIDDM > 5 years is associated with increased prevalence of microalbuminuria, and hypertension is associated with microalbuminuria and clinical proteinuria in this population.

Dimensionality of an early childhood scale using rasch analysis and confirmatory factor analysis.

This paper explores the use of Rasch analysis and linear confirmatory factor analysis as methods for investigating the dimensionality of an early childhood test (Gesell School Readiness Screening Test), taking into account the theoretical basis of test construction. The paper presents the results of empirical analyses using both approaches and discusses the theoretical and psychometric considerations that guide the selection and application of each technique.

Long-term normoglycemic remission in black newly diagnosed NIDDM subjects.

We have defined and characterized the natural history of spontaneous near-normoglycemic remission off of antidiabetic medication in 79 black NIDDM subjects. They had initially presented with plasma glucose levels of 37.8 +/- 19.3 mmol/l. Baseline clinical metabolic and 8-year prospective data were obtained (51 men and 28 women, mean age 45 +/- 10 years, islet-cell or GAD antibody negative). After hospitalization and intensive outpatient treatment, near-normoglycemic remission (fasting plasma glucose 6.1 +/- 0.83 mmol/l and HbA1c 0.95 +/- 0.10 of upper limit of normal) occurred within 8 +/- 10 months of insulin or sulfonylurea therapy. This was unrelated to the resolution of stress or significant weight loss (1.9 +/- 4.97 kg). Metabolic studies performed during remission showed 17% normal, 33% impaired, and 50% diabetic glucose tolerance. Glucose disposal (1 mU x kg-1 x min-1) euglycemic insulin clamp with D-[3(-3)H]glucose) was higher in the normal glucose tolerance group compared with the impaired and diabetic groups (37.8 +/- 10.2 vs. 26.1 +/- 10.7 and 26.7 +/- 12.0 micromol x kg-1 x min-1; P < 0.05) despite similar BMIs in all three groups (28.8 +/- 3.7 kg/m2). Insulin secretion was below the normal range. Of 79 patients, 27 relapsed. A Kaplan-Meier survival analysis gives a median time of 40 months to relapse. Higher presenting plasma glucose and male sex predicted earlier relapse. Near-normoglycemic remission may occur in up to 30% of black new-onset NIDDM patients. It appears to be associated with intensive initial glycemic regulation and may be a method of decreasing the development of microvascular complications in NIDDM.