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Ananda Basu

Publications and source records attributed to Ananda Basu.

27 records · Page 2Linked to original sources
PubMed2003

Insulin sensitizers.

Type 2 diabetes mellitus is an increasingly prevalent disorder associated with multiple metabolic derangements. Insulin resistance is the most prominent feature common in both type 2 diabetes and its associated metabolic abnormalities. Until 1995, the only therapeutic interventions available in the United States were the insulin secretagogues sulfonylureas and insulin. With the introduction of metformin in the United States in the mid-1990s and the subsequent advent of thiazolidinediones, an opportunity exists to address and directly reverse, at least in part, the defects in insulin action seen in individuals with type 2 diabetes. Evidence shows that insulin sensitizers not only have beneficial effects on glycemic control but also have multiple effects on lipid metabolism and atherosclerotic vascular processes that could prove to be beneficial. We discuss safety issues of these agents, their potential use in preventing onset and progression of diabetes, and their use in other related metabolic conditions such as polycystic ovary syndrome.

Biguanides↗
PubMed2002

Effect of enteral vs. parenteral glucose delivery on initial splanchnic glucose uptake in nondiabetic humans.

To determine if enteral delivery of glucose influences splanchnic glucose metabolism, 10 subjects were studied when glucose was either infused into the duodenum at a rate of 22 micromol x kg(-1) x min(-1) and supplemental glucose given intravenously or when all glucose was infused intravenously while saline was infused intraduodenally. Hormone secretion was inhibited with somatostatin, and glucose (approximately 8.5 mmol/l) and insulin (approximately 450 pmol/l) were maintained at constant but elevated levels. Intravenously infused [6,6-(2)H(2)]glucose was used to trace the systemic appearance of intraduodenally infused [3-(3)H]glucose, whereas UDP-glucose flux (an index of hepatic glycogen synthesis) was measured using the acetaminophen glucuronide method. Despite differences in the route of glucose delivery, glucose production (3.5 +/- 1.0 vs. 3.3 +/- 1.0 micromol x kg(-1) x min(-1)) and glucose disappearance (78.9 +/- 5.7 vs. 85.0 +/- 7.2 micromol x kg(-1) x min(-1)) were comparable on intraduodenal and intravenous study days. Initial splanchnic glucose extraction (17.5 +/- 4.4 vs. 14.5 +/- 2.9%) and hepatic UDP-glucose flux (9.0 +/- 2.0 vs. 10.3 +/- 1.5 micromol x kg(-1) x min(-1)) also did not differ on the intraduodenal and intravenous study days. These data argue against the existence of an "enteric" factor that directly (i.e., independently of circulating hormone concentrations) enhances splanchnic glucose uptake or hepatic glycogen synthesis in nondiabetic humans.

Adult↗
PubMed2002

Insulinoma in chronic renal failure: a case report.

The diagnosis of insulinoma depends on the fulfillment of well-established criteria during the 72-h fast. However, these criteria rely on normal renal function. Spontaneous hypoglycemia that is not attributable to insulinoma may occur in persons with renal failure. We describe herein a patient with renal impairment who had undergone renal transplant and had a 20-yr history of hypoglycemic symptoms and successful resection of insulinoma. Although the results of a 72-h fast were consistent with endogenous hyperinsulinemia, their interpretation was complicated in the presence of renal impairment. Fortunately, the identification of the tumor, by endoscopic ultrasonograph, led to a correct diagnosis. This case seems to be the second report of a patient with insulinoma with concomitant renal failure.

Humans↗
PubMed2002

Effects of free fatty acids and glycerol on splanchnic glucose metabolism and insulin extraction in nondiabetic humans.

The present study sought to determine whether elevated plasma free fatty acids (FFAs) alter the ability of insulin and glucose to regulate splanchnic as well as muscle glucose metabolism. To do so, FFAs were increased in 10 subjects to approximately 1 mmol/l by an 8-h Intralipid/heparin (IL/Hep) infusion, whereas they fell to levels near the detection limit of the assay (<0.05 mmol/l) in 13 other subjects who were infused with glycerol alone at rates sufficient to either match (n = 5, low glycerol) or double (n = 8, high glycerol) the plasma glycerol concentrations observed during the IL/Hep infusion. Glucose was clamped at approximately 8.3 mmol/l, and insulin was increased to approximately 300 pmol/l to stimulate both muscle and hepatic glucose uptake. Insulin secretion was inhibited with somatostatin. Leg and splanchnic glucose metabolism were assessed using a combined catheter and tracer dilution approach. Leg glucose uptake (21.7 +/- 3.5 vs. 48.3 +/- 9.3 and 57.8 +/- 11.7 micromol x kg(-1) leg x min(-1)) was lower (P < 0.001) during IL/Hep than the low- or high-glycerol infusions, confirming that elevated FFAs caused insulin resistance in muscle. IL/Hep did not alter splanchnic glucose uptake or the contribution of the extracellular direct pathway to UDP-glucose flux. On the other hand, total UDP-glucose flux (13.2 +/- 1.7 and 12.5 +/- 1.0 vs. 8.1 +/- 0.5 micromol x kg(-1) x min(-1)) and flux via the indirect intracellular pathway (8.4 +/- 1.2 and 8.1 +/- 0.6 vs. 4.8 +/- 0.05 micromol x kg(-1) x min(-1)) were greater (P < 0.05) during both the IL/Hep and high-glycerol infusions than the low-glycerol infusion. In contrast, only IL/Hep increased (P < 0.05) splanchnic glucose production, indicating that elevated FFAs impaired the ability of the liver to autoregulate. Splanchnic insulin extraction, directly measured using the arterial and hepatic vein catheters, did not differ (67 +/- 3 vs. 71 +/- 5 vs. 69 +/- 1%) during IL/Hep and high- and low-glycerol infusions. We conclude that elevated FFAs exert multiple effects on glucose metabolism. They inhibit insulin- and glucose-induced stimulation of muscle glucose uptake and suppression of splanchnic glucose production. They increase the contribution of the indirect pathway to glycogen synthesis and impair hepatic autoregulation. On the other hand, they do not alter either splanchnic glucose uptake or splanchnic insulin extraction in nondiabetic humans.

Adult↗
PubMed2002

Posttransplantation diabetes: a systematic review of the literature.

OBJECTIVES: To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS: We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS: Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (<10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS: Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs.

Databases, Bibliographic↗
PubMedDate not supplied

Insulin autoimmunity and hypoglycemia in seven white patients.

OBJECTIVE: To report the clinical, biochemical, and immunologic characteristics of 7 white patients with the rare disorder of hyperinsulinemic hypoglycemia in association with spontaneously generated high titers of antibodies to human insulin. METHODS: We reviewed the clinical data, history, and symptoms of the 7 study patients and summarized the biochemical findings during a spontaneous episode of hypoglycemia. Insulin antibody binding was measured in all patients, and antibody affinity, capacity, and clonality were analyzed in 4. A mixed meal study was conducted in 2 patients. A potential mechanism for postprandial hypoglycemia is presented. RESULTS: In all 7 patients (6 women and 1 man), symptoms were neuroglycopenic, occurring primarily postprandially but during fasting in some patients. During hypoglycemia, concentrations of insulin, proinsulin, and, in most patients, C peptide considerably exceeded those observed in patients with insulinoma. These concentrations were spuriously elevated as a result of interference by the autoantibodies in the immunoassays. No patient had evidence of an insulinoma on various radiologic localization procedures directed at the pancreas. Insulin antibodies showed a high percentage of binding to human insulin--50 to 90%. Heterogeneity of antibodies regarding clonality and antibody binding sites was noted; some patients had polyclonal and some had monoclonal IgG class antibodies. Most patients had two categories of binding sites: high affinity/low capacity and low capacity/high affinity. Although the mechanism for postprandial hypoglycemia remains conjectural, prolonged elevations of postprandial concentrations of total and free insulin are consistent with the putative mechanism of a buffering effect of insulin antibodies. CONCLUSION: Insulin autoimmune hypoglycemia, although rare in any racial group and especially in white subjects, can be readily detected by high titers of insulin antibodies. Such a determination should be done in all patients undergoing evaluation for hypoglycemia.

Aged↗