Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance.

AIMS: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. METHODS: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence.

A quantitative measure of diabetes risk in community practice impacts clinical decisions: the PREVAIL initiative.

BACKGROUND AND AIMS: While predictive tools are being developed to identify those at highest risk for developing diabetes, little is known whether these assays affect clinical care. METHODS AND RESULTS: Thirty sites who used the PreDx(®) (Tethys BioScience, Emeryville, CA) abstracted clinical information from baseline clinic visits prior to a PreDx test and from the most recent visit at time of abstraction. All visits occurred between May 2008-April 2011 (median follow-up 198 days, IQR 124-334). The primary analysis was the influence of the PreDx test (5-year diabetes prediction) on subsequent care; descriptive statistics were used to summarize baseline and follow-up variables. Overall 913 patients with 2 abstracted visits were included. Relative to baseline, median SBP decreased 1.5 mmHg (p = 0.039), DBP decreased 2 mmHg (p < 0.001), LDL-C decreased 4 mg/dL (p = 0.009), and HDL-C increased 2 mg/dL (p < 0.001) at follow-up. Behavioral or lifestyle counseling was not significantly different from baseline to follow-up (71.2% vs. 68.1% (p = 0.077), but BMI was lower by 0.2 kg/m(2) at follow up (p = 0.013). At follow-up, more patients were prescribed metformin (13.7% vs. 9.7%, p < 0.001). A higher PreDx score was significantly associated with metformin prescription (p = 0.0003), lifestyle counseling (p = 0.0099), and a lower BMI at follow-up (p = 0.007). CONCLUSION: The use of a prognostic test in patients perceived to be high risk for diabetes was associated with a modest but significant increase in the prescription of metformin and lifestyle interventions and a reduction in BMI.

Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study.

AIMS: Whether long-term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long-term differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group. METHODS: This long-term follow-up (median 10 years, interquartile range 9.0-10.5) of the three-arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1-year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow-up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually. RESULTS: After 10 years' follow-up from Diabetes Prevention Program baseline, major reductions were seen for systolic (-2 to -3) and diastolic (-6 to -6.5 mmHg) blood pressure, and for LDL cholesterol (-0.51 to -0.6 mmol/l) and triglycerides (-0.23 to -0.25 mmol/l) in all groups, with no between-group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study. CONCLUSION: Overall, intensive lifestyle intervention achieved, with less medication, a comparable long-term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.

Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials.

AIM: Hypoglycaemia and the fear of hypoglycaemia are barriers to achieving normoglycaemia with insulin. Insulin degludec (IDeg) has an ultra-long and stable glucose-lowering effect, with low day-to-day variability. This pre-planned meta-analysis aimed to demonstrate the superiority of IDeg over insulin glargine (IGlar) in terms of fewer hypoglycaemic episodes at equivalent HbA1c in type 2 and type 1 diabetes mellitus (T2DM/T1DM). METHODS: Pooled patient-level data for self-reported hypoglycaemia from all seven (five in T2DM and two in T1DM) randomized, controlled, phase 3a, treat-to-target trials in the IDeg clinical development programme comparing IDeg once-daily (OD) vs. IGlar OD were analysed. RESULTS: Four thousand three hundred and thirty subjects (2899 IDeg OD vs. 1431 IGlar OD) were analysed. Among insulin-naïve T2DM subjects, significantly lower rates of overall confirmed, nocturnal confirmed and severe hypoglycaemic episodes were reported with IDeg vs. IGlar: estimated rate ratio (RR):0.83[0.70;0.98](95%) (CI) , RR:0.64[0.48;0.86](95%) (CI) and RR:0.14[0.03;0.70](95%) (CI) . In the overall T2DM population, significantly lower rates of overall confirmed and nocturnal confirmed episodes were reported with IDeg vs. IGlar [RR:0.83[0.74;0.94](95%) (CI) and RR:0.68[0.57;0.82](95%) (CI) ). In the T1DM population, the rate of nocturnal confirmed episodes was significantly lower with IDeg vs. IGlar during maintenance treatment (RR:0.75[0.60;0.94](95%) (CI) ). Reduction in hypoglycaemia with IDeg vs. IGlar was more pronounced during maintenance treatment in all populations. CONCLUSIONS: The limitations of this study include the open-label design and exclusion of subjects with recurrent severe hypoglycaemia. This meta-analysis confirms that similar improvements in HbA1c can be achieved with fewer hypoglycaemic episodes, particularly nocturnal episodes, with IDeg vs. IGlar across a broad spectrum of patients with diabetes.

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.

Improved health status with insulin degludec compared with insulin glargine in people with type 1 diabetes.

AIMS: The efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed. METHODS: Degludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains. RESULTS: At study end, HbA(1c) reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.25-0.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.52-1.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.32-5.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.89-14.18)] and mental health domains [+2.46 (95% CI 0.10-4.82)]. For mental component score, Cohen's effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI -2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine. CONCLUSIONS: In the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events.

Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial.

AIMS: To evaluate the dose-response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. METHODS: Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA(1c)) > or = 7.0 and < 9.0% (> or = 53 and < 75 mmol/mol)] on metformin (> or = 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 microg once daily or twice daily or placebo. The primary end-point was change in HbA(1c) from baseline to 13 weeks in the intent-to-treat population. RESULTS: Lixisenatide significantly improved mean HbA(1c) from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 microg doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA(1c) < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 microg once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from -2.0 to -3.9 kg with lixisenatide vs. -1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. CONCLUSIONS: Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose-response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 microg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies.

Persistent cutaneous insulin allergy resulting from high-molecular-weight insulin aggregates.

Cutaneous insulin allergy remains a clinical problem despite the use of highly purified human insulins. We used in vitro lymphocyte-transformation studies to examine the reactivity of various insulin formulations in diabetic patients with (n = 4) and without (n = 8) cutaneous allergies. Nonspecific response to concanavalin A demonstrated a greater than 40-fold response in both groups. Control patients did not respond to the addition of commercial insulin preparations (stimulation index [SI] less than 4), whereas allergic patients had an 11-fold response to beef (P less than 0.01), a 10-fold response to pork (P less than 0.01), and a 6-fold response to human (P less than 0.01) insulins. This response was limited to a single insulin manufacturer's preparations and was uniform in all three species tested. Efforts to identify the offending agent revealed no lymphoblast transformation when crystalline insulin was used or when commercial preparations were purified to a single peak by high-performance liquid chromatography (HPLC). Pure crystalline insulin dimers of beef, pork, and human species were tested; control subjects responded with mean SIs of 1.9, 1.9, and 1.8, respectively, whereas allergic patients showed greater reactivity to beef (SI 7.3) and pork (SI 14.8). The lymphoblast-transformation response to crystalline human dimer was dose dependent with mean SIs of 0.9 at low concentration (2.8 ng/ml) and 19.2 at a higher concentration (20.4 ng/ml). The commercial insulin preparations were run on size-exclusion HPLC to determine high-molecular-weight aggregate content. Independent of species, a single manufacturer had products demonstrating aggregate levels 3- to 6-fold higher than those found in other manufacturers' preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Are insulin and proinsulin independent risk markers for premature coronary artery disease ?

Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin levels with the likelihood of a patient having or not having CAD disappears after adjustment for BMI, suggesting that insulin and proinsulin are not independent risk markers but are primarily dependent on obesity.

Motor vehicles, hypoglycemia, and diabetic drivers.

Individuals with diabetes are increasingly persuing employment in fields previously restricted as a result of the development of chronic complications. Improved glycemic control resulting from use of sophisticated insulin delivery and monitoring systems has also led to the recognition of recurrent hypoglycemia as a potential major clinical and occupational hazard. No data concerning the occupational safety of individuals with insulin-treated diabetes mellitus (ITDM) are available. We review the literature on diabetic drivers in an effort to examine the impact of certification of ITDMs as commercial drivers. In the absence of significant worldwide experience with ITDMs as commercial drivers, the discussion is necessarily based on projected accident rates derived from data on frequency of hypoglycemia. These studies are universally flawed by variable definitions of hypoglycemia, ascertainment bias, and patient selection. They do, however, provide a worst-case/best-case scenario for discussion. It is imperative that any expansion of employment opportunities for ITDMs be followed carefully with prospective studies to assess the impact on public safety.

Unrecognized diabetes among hospitalized patients.

OBJECTIVE: To evaluate the hospital care rendered to hyperglycemic individuals who did not have a diagnosis of diabetes before admission. RESEARCH DESIGN AND METHODS: A total of 1,034 consecutively hospitalized adult patients at a 750-bed inner-city teaching hospital were evaluated. Patients with one or more plasma glucose values > 200 mg/dl were identified by the laboratory data system on a daily basis. Patients without a diagnosis of diabetes at the time of admission were evaluated to determine if and how physicians addressed the hyperglycemia, whether a new diagnosis of diabetes was made during admission, and whether follow-up was planned to address the hyperglycemia. RESULTS: After excluding patients who were admitted for a primary diagnosis of diabetes, 37.5% of all hyperglycemic medical patients and 33% of hyperglycemic surgical patients were without a diagnosis of diabetes at the time of admission. These patients had a mean peak glucose of 299 mg/dl, and 66% had two or more elevated values during their hospitalization. Fifty-four percent received insulin therapy, and 59% received bedside glucose monitoring, yet 66% of daily patient progress notes failed to comment on the presence of hyperglycemia or diabetes. Diabetes was documented in only three patients (7.3%) as a possible diagnosis in the daily progress notes. CONCLUSIONS: Despite marked hyperglycemia, most medical records made no reference to the possibility of unrecognized diabetes. Given the average delay of a decade between the onset and diagnosis of type 2 diabetes, further evaluation of hyperglycemic hospitalized patients may present an important opportunity for earlier detection and the initiation of therapy.

Effect of physician specialty on outcomes in diabetic ketoacidosis.

OBJECTIVE: More than 100,000 people are hospitalized annually in the U.S. with diabetic ketoacidosis (DKA). Outcome differences have not been examined for these patients based on whether their primary care provider is a generalist or a diabetes specialist. The objective of this study was to investigate hospital charges and hospital length of stay (LOS) for patients with DKA according to the specialty of their primary care provider. RESEARCH DESIGN AND METHODS: We investigated all patients with a primary diagnosis of DKA during a 3.5-year period (n = 260) in a large urban teaching hospital. Hospital charges and LOS were studied regarding the specialty of the primary care provider. Demographic factors, severity of illness, laboratory data, and readmission rates were compared. RESULTS: Patients cared for by generalists and endocrinologists had a similar case mix and severity of DKA. The age-adjusted mean LOS for patients of generalists was 4.9 days (95% CI 4.5-5.4), and the mean LOS for patients of endocrinologists was 3.3 days (2.6-4.2) (P < 0.0043). Mean hospital charges differed (P < 0.0001) with an age- and sex-adjusted mean for patients of endocrinologists of $5,463 ($4,179-7,141) and a mean for patients of generalists of $10,109 ($9,151-11,166). The additional charges incurred by generalists were due in part to patients undergoing more procedures. No differences in diabetes-related complications occurred during admission, but the endocrinologist-treated group had a lower readmission rate for DKA during the study period than the generalist-treated group (2 vs. 6%, respectively) (P = 0.03). CONCLUSIONS: Endocrinologists provide more cost-effective care than generalists do when serving as primary care providers for patients hospitalized with DKA.

Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes.

OBJECTIVE: Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin. RESEARCH DESIGN AND METHODS: This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l. RESULTS: A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin. CONCLUSIONS: Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.

The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up.

CONTEXT: Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM. OBJECTIVE: The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study. DESIGN: This was a randomized controlled clinical trial with an observational follow-up. SETTING: The study was conducted at 27 clinical centers. PARTICIPANTS: Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry. INTERVENTIONS: Interventions included placebo, ILS, or metformin. OUTCOMES MEASURE: Outcomes measure was diabetes mellitus. RESULTS: Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. CONCLUSIONS: Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes.

Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone.

PURPOSE: To assess the status of the hypothalamic-pituitary-adrenal (HPA) axis in cortico-steroid-treated patients whose prednisone dose had been tapered to physiologic doses. PATIENTS AND METHODS: The design of the study was a retrospective chart review of 50 consecutive patients receiving 10 mg or less of prednisone daily at a university teaching hospital rheumatology clinic. Patients were given a rapid adrenocorticotropic hormone stimulation test, with cortisol levels obtained at baseline and after intravenous administration of cosyntropin. Charts were reviewed for duration of therapy, highest, current, and total cumulative steroid dose, and average daily steroid dose in each month of the preceding 2 years. RESULTS: Current steroid dose was the only significant indicator of HPA axis function. Patients receiving less than 5 mg of prednisone daily had a normal HPA axis response, whereas those receiving 5 mg or more had widely varied responses. Neither the total, the highest prednisone dose, nor the duration of therapy was a significant indicator of HPA axis recovery. CONCLUSIONS: Spontaneous recovery of the HPA axis is usual for patients who are taking prednisone at daily doses of 5 mg or less. Return of normal HPA axis function can be achieved without alternate-day therapy in patients whose disease allows tapering to daily prednisone doses of 5 mg or less.

Autoantibodies to the insulin receptor as a cause of autoimmune hypoglycemia in systemic lupus erythematosus.

A 52-year-old black woman presented with clinical features of systemic lupus erythematosus (SLE) and severe fasting hypoglycemia. Hypoglycemia was secondary to autoantibodies to the insulin receptor that were detected in the patient's serum. There were no anti-insulin antibodies, and other causes of hypoglycemia were excluded. Treatment with high-dose glucocorticoids resulted in restoration of euglycemia associated with resolution of circulating anti-receptor antibodies and parallel improvement in clinical and laboratory features of SLE. This case is compared with other cases of autoimmune hypoglycemia due to anti-receptor antibodies.

Successful long-term kidney-pancreas transplants in diabetic patients with high C-peptide levels.

BACKGROUND: Pancreas transplants are rarely done in type 2 (noninsulin dependent) diabetic patients. Most researchers believe that in type 2 diabetic patients, peripheral insulin resistance plays a central role and also is associated with relative insulin deficiency or an insulin secretory defect. This suggests that in patients receiving transplants, the new beta cells will be overstimulated, leading to beta cell "exhaustion" and graft failure. METHODS: Early in our experience, simultaneous pancreas-kidney transplant candidates were selected using only clinical criteria for type 1 diabetes, i.e., early onset of diabetes and rapid onset of insulin use. Pretransplant sera were available for C-peptide analysis in 70 of 94 of those patients. Forty-four percent (31/70) were African American (AA). RESULTS: Thirteen patients (12 AA) with a nonfasting C-peptide level >1.37 ng/ml were identified. In these patients with high C-peptide levels, pancreas and kidney survival rates were 10O%. The results did not differ statistically from the low C-peptide group (< or =1.37 ng/ ml). There were no differences between patient and pancreas-kidney survival rates when the patients were separated into AA and non-AA groups. The follow-up was 1-89 months, with a mean of 45.5 months. CONCLUSIONS: Long-term pancreas graft function is attainable and beta cell "exhaustion" does not occur in patients with high preoperative C-peptide (>1.37 ng/ ml) levels. AA and non-AA patients have equivalent long-term patient, kidney, and pancreas-kidney graft survival rates.

Long-term health care outcomes in diabetes. Economic and political implications.

With building pressure for cost-containment of medical expenditures, the medical community is finding it increasingly necessary to justify its procedures and systems of care. The analysis of health care outcomes has been extensively applied to diabetes care as a means of determining the process by which optimal outcomes may be achieved. This article reviews basic concepts of outcomes analysis, with differentiation between process measures and outcome measures. A review of the available outcome literature as it pertains to diabetes also is provided.

Controlling postprandial hyperglycemia.

A growing body of evidence indicates that measurements of postprandial glucose levels, in combination with glycosylated hemoglobin, are a more accurate predictor of metabolic abnormality than fasting or preprandial glucose levels for individuals with type 2 diabetes. Early identification of elevated postprandial blood glucose levels is an important step in predicting the onset of microvascular and macrovascular complications that can progress to full symptomatic diabetes. This article summarizes the research conducted to date on the diagnostic import of postprandial glucose and the parameters established for judging the need for treatment. When individuals cannot reach target glucose levels through diet and exercise, medical treatment is necessary. The article reviews a range of treatment options, including insulin secretagogues, insulin sensitizers, antiabsorptive agents, weight reduction agents, and insulin and combination medical therapy.

Secretion of prolactin after acute and chronic stimulation of the breast: effect of timing during the menstrual cycle.

The effect of acute and chronic stimulation of the breast was studied in 11 nonpostpartum women in both follicular and luteal phases of menstruation. In no subject did an increase in secretion of prolactin (PRL) result from either solitary or multiple episodes of stimulation of the breast over 24 hours. After 2 weeks of stimulation, three patients noted increased secretion; however, on rechallenge, this was found to be the result of testing in luteal versus follicular phase, rather than of the stimulation of breast itself. We concluded that breast stimulation, either acute or chronic, had no appreciable impact on secretion of PRL, but, rather, the phase of menstruation may influence basal secretion of PRL. Normal ranges may have to be recalculated to take this into account after larger numbers of women are studied.