Citations

OBJECTIVE—Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia. We conducted a randomized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS—To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin, 22 individuals (aged 44 ± 14 years [±SD], 55% men) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of <7.8% were randomized in a crossover design to receive either glargine or ultralente as the basal insulin for 4 months. Aspart insulin was used as the prandial insulin. Physicians providing insulin dose adjustment advice were masked to the type of basal insulin. RESULTS—Treatment with glargine resulted in lower mean HbA1c (6.82 ± 0.13 vs. 7.02 ± 0.13, difference: 0.2 ± 0.08, P = 0.026), less nocturnal variability (plasma glucose 49.06 ± 4.74 vs. 62.36 ± 5.21 mg/dl, P = 0.04), and less hypoglycemia (24.5 ± 2.99 vs. 31.3 ± 4.04 events, P = 0.05), primarily due to less daytime hypoglycemia (P = 0.002). On the other hand, serious hypoglycemia and average glucose concentration measured with continuous subcutaneous glucose monitoring did not differ. CONCLUSIONS—We conclude that while use of either ultralente or glargine as a basal insulin can result in excellent glycemic control, treatment with glargine is associated with slightly but significantly lower HbA1c and less nocturnal glycemic variability and hypoglycemia.

OBJECTIVE—To determine the efficacy of telecare (modem transmission of glucometer data and clinician feedback) to support intensive insulin therapy in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS—Thirty-one patients with type 1 diabetes on intensive insulin therapy and with HbA1c >7.8% were randomized to telecare (glucometer transmission with feedback) or control (glucometer transmission without feedback) for 6 months. The primary end point was 6-month HbA1c. To place our findings in context, we pooled HbA1c change from baseline reported in randomized trials of telecare identified in a systematic review of the literature. RESULTS—Compared with the control group, telecare patients had a significantly lower 6-month HbA1c (8.2 vs. 7.8%, P = 0.03, after accounting for HbA1c at baseline) and a nonsignificant fourfold greater chance of achieving 6-month HbA1c ≤7% (29 vs. 7%; risk difference 21.9%, 95% CI −4.7 to 50.5). Nurses spent 50 more min/patient giving feedback on the phone with telecare patients than with control patients. Meta-analysis of seven randomized trials of adult patients with type 1 diabetes found a 0.4% difference (95% CI 0–0.8) in HbA1c mean change from baseline between the telecare and control groups. CONCLUSIONS—Telecare is associated with small effects on glycemic control in patients with type 1 diabetes on intensive insulin therapy but with inadequate glycemic control.

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.

OBJECTIVE—To demonstrate the strong association of diabetic mastopathy or sclerosing lymphocytic lobulitis with type 1 diabetes mellitus by studying appropriate control groups and to describe risk factors and natural history of the disorder. RESEARCH DESIGN AND METHODS—This was a retrospective cross-sectional study of four groups of patients conducted at a setting tertiary care medical center. We examined benign breast biopsies (investigator masked to identity) from age-matched patients with types 1 and 2 diabetes, autoimmune thyroid disease, or none of the above disorders for sclerosing lymphocytic lobulitis. Several risk factors proposed for the disorder (age at diagnosis of benign breast disease, duration of diabetes, age at onset of diabetes, prevalence of retinopathy, neuropathy, nephropathy and cheiroarthropathy, glycemic control, parity, oral contraceptive use, menopausal status, or number of breast biopsies) were evaluated, and patients were contacted to describe the natural history of the disorder. RESULTS—Sclerosing lymphocytic lobulitis was identified in 69.7% of the subjects with type 1 diabetes and 1.8% of those with autoimmune thyroid disease diagnosed with benign breast disease at surgery. It did not occur in patients with type 2 diabetes with or without insulin treatment or in control subjects. Only retinopathy and peripheral neuropathy were associated with sclerosing lymphocytic lobulitis. Breast carcinoma or lymphoma did not occur subsequently in any type 1 diabetes patient with or without sclerosing lymphocytic lobulitis. CONCLUSIONS—Sclerosing lymphocytic lobulitis is strongly associated with type 1 diabetes. Retinopathy and neuropathy are associated with the disorder. The risk of malignancy is not increased.

Melanin concentrating hormone (MCH) is a hypothalamic neuropeptide known to play a critical role in energy balance. We have previously reported that overexpression of MCH is associated with mild obesity. In addition, mice have substantial hyperinsulinemia and islet hyperplasia that is out of proportion with their degree of obesity. In this study, we further explored the role of MCH in the endocrine pancreas. Both MCH and MCHR1 are expressed in mouse and human islets and in clonal β-cell lines as assessed using quantitative real-time PCR and immunohistochemistry. Mice lacking MCH (MCH-KO) on either a C57Bl/6 or 129Sv genetic background showed a significant reduction in β-cell mass and complemented our earlier observation of increased β-cell mass in MCH-overexpressing mice. Furthermore, the compensatory islet hyperplasia secondary to a high-fat diet, which was evident in wild-type controls, was attenuated in MCH-KO. Interestingly, MCH enhanced insulin secretion in human and mouse islets and rodent β-cell lines in a dose-dependent manner. Real-time PCR analyses of islet RNA derived from MCH-KO revealed altered expression of islet-enriched genes such as glucagon, forkhead homeobox A2, hepatocyte nuclear factor (HNF)4α, and HNF1α. Together, these data provide novel evidence for an autocrine role for MCH in the regulation of β-cell mass dynamics and in islet secretory function and suggest that MCH is part of a hypothalamic-islet (pancreatic) axis.