Mary E. Larkin

Measuring psychological insulin resistance: barriers to insulin use.

PURPOSE The purpose of this study is to explore the attitudes that contribute to psychological insulin resistance (PIR) in insulin-naive patients with type 2 diabetes and to identify predictors of PIR. METHODS A prospective study using 2 self-report surveys and incorporating demographic and health variables was conducted to determine the prevalence of PIR among a sample of 100 adult, insulin-naive patients with type 2 diabetes at an outpatient diabetes center in a university-affiliated teaching hospital. RESULTS Thirty-three percent of patients with type 2 diabetes were unwilling to take insulin. The most commonly expressed negative attitudes were concern regarding hypoglycemia, permanent need for insulin therapy, less flexibility, and feelings of failure. Less than 40% expressed fear of self-injection or thought that injections were painful. However, compared with willing subjects, unwilling subjects were more likely to fear injections and thought injections would be painful, life would be less flexible, and taking insulin meant health would deteriorate (P< .005 for all comparisons). Poorer general health and higher depression scores also correlated with PIR. CONCLUSIONS The results of the surveys, which were generally consistent, identified several remediable misconceptions regarding insulin therapy and suggest targets for educational interventions.

Glycemic control in diabetes mellitus: have changes in therapy made a difference?

PURPOSE New methods of measuring and controlling glycemia in diabetes mellitus have been developed and implemented in the past 10 years. We examined whether glycemia, as measured by glycosylated hemoglobin, changed in outpatient insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) populations between 1985 and 1993 and whether contemporaneous changes in therapy could account for observed changes in glycemia. PATIENTS AND METHODS Outpatients were selected based on having glycated hemoglobin (HbA1c) measured in the Massachusetts General Hospital laboratory during March 1985 (IDDM n = 94 and NIDDM n = 137) or during March 1993 (IDDM n = 89 and NIDDM n = 118). Chart reviews established demographic and clinical characteristics, including frequency of blood glucose self-monitoring, insulin injections, office visits, and HbA1c measurements during the year prior to the HbA1c result. RESULTS Mean HbA1c level was significantly lower in the 1993 IDDM cohort compared with the 1985 cohort (8.77% +/- 1.7% versus 9.47% +/- 2.1%, P = 0.014). In the NIDDM cohorts, the difference in mean HbA1c did not achieve statistical significance (8.35% +/- 1.6% in 1993 versus 8.75% +/- 2.1% in 1985, P = 0.09); however, when adjusted for differences in NIDDM duration, HbA1c in the 1993 cohort was significantly lower than that in the 1985 cohort. The largest decrease in HbA1c in NIDDM was in patients treated with insulin (9.53% +/- 2.0% versus 8.54% +/- 1.5% in 1985 and 1993, respectively, P = 0.004). Multiple linear regression analyses demonstrated that increased frequency of self-monitoring and of insulin injections were associated with lower HbA1c in IDDM. CONCLUSIONS The level of average glycemia has decreased in IDDM patients over the past 8 years, attributable, at least in part, to an increased frequency of monitoring and of insulin injections. Glycemia decreased in NIDDM, especially in the subset of patients treated with insulin. This temporal shift in glycemic control should have a salutary effect on the development of long-term microvascular and neurologic complications.

The Long-Term Effects of Type 1 Diabetes Treatment and Complications on Health-Related Quality of Life: A 23-year follow-up of the Diabetes Control and Complications/Epidemiology of Diabetes Interventions and Complications cohort

OBJECTIVE To examine the long-term effects of type 1 diabetes treatment, metabolic control, and complications on health-related quality of life (HRQOL). RESEARCH DESIGN AND METHODS A total of 1,441 participants, initially 13–39 years of age, were followed for an average of 23.5 years as part of the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. The Diabetes Quality-of-Life questionnaire (DQOL) was administered annually during DCCT and every other year during EDIC. Biomedical data, including HbA1c levels, exposure to severe hypoglycemia, intercurrent psychiatric events, and development of diabetes complications were collected at regular intervals throughout the follow-up. RESULTS Mean total DQOL scores were not significantly different between the former DCCT intensive and conventional treatment groups (DCCT baseline, 78 ± 8 vs. 78 ± 9; EDIC year 17, 75 ± 11 vs. 74 ± 11). Over the course of the study, a drop of ≥5 points in DQOL score from DCCT baseline maintained on two successive visits occurred in 755 individuals and was associated with increased HbA1c, albumin excretion rate, mean blood pressure, BMI, and occurrence of hypoglycemic events requiring assistance. Lower DQOL scores after 23.5 years of follow-up were associated with prior development of retinopathy (P = 0.0196), nephropathy (P = 0.0019), and neuropathy (P < 0.0001) as well as self-reported chest pain (P = 0.0004), decreased vision in both eyes (P = 0.0005), painful paresthesias (P < 0.0001), recurrent urinary incontinence (P = 0.0001), erectile dysfunction (P < 0.0001), and history of psychiatric events (P < 0.0001). CONCLUSIONS Among DCCT/EDIC participants, worsening metabolic control, serious diabetes complications and their associated symptoms, and development of psychiatric conditions led to decreased HRQOL.

Triglyceride levels affect cognitive function in noninsulin-dependent diabetics

Noninsulin-dependent diabetes mellitus (NIDDM) is associated with decrements in several cognitive functions. Among the variables that apparently contribute to the decline in cognitive performance is poor glucose control, as measured by hemoglobin A1c. Elevated levels of triglycerides in diabetics may also contribute to this cognitive decline through the increased incidence of atherosclerosis in these patients. The authors examined the relationship between triglycerides and cognitive performance in 246 NIDDM outpatients, aged 55-74 years. The relationship between triglyceride levels and performance on three cognitive tasks and on a test of reaction time was measured. Elevated levels of triglycerides were associated with significant decrements in performance on the digit symbol substitution test, digit span (backward) test, and on a reaction time measure. High levels of triglycerides, independent of chronic glucose control, appear to contribute to the decreased ability to perform short-term memory tasks in NIDDM.

Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients**

PURPOSE To examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy. PATIENTS AND METHODS Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n=6; or intravenously, n=2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal. RESULTS Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fishers two-tailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration. CONCLUSIONS The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia.

Regression From Prediabetes to Normal Glucose Regulation Is Associated With Reduction in Cardiovascular Risk: Results From the Diabetes Prevention Program Outcomes Study

OBJECTIVE Restoration of normal glucose regulation (NGR) in people with prediabetes significantly decreases the risk of future diabetes. We sought to examine whether regression to NGR is also associated with a long-term decrease in cardiovascular disease (CVD) risk. RESEARCH DESIGN AND METHODS The Framingham (2008) score (as an estimate of the global 10-year CVD risk) and individual CVD risk factors were calculated annually for the Diabetes Prevention Program Outcomes Study years 1–10 among those patients who returned to NGR at least once during the Diabetes Prevention Program (DPP) compared with those who remained with prediabetes or those in whom diabetes developed during DPP (N = 2,775). RESULTS The Framingham scores by glycemic exposure did not differ among the treatment groups; therefore, pooled estimates were stratified by glycemic status and were adjusted for differences in risk factors at DPP baseline and in the treatment arm. During 10 years of follow-up, the mean Framingham 10-year CVD risk scores were highest in the prediabetes group (16.2%), intermediate in the NGR group (15.5%), and 14.4% in people with diabetes (all pairwise comparisons P < 0.05), but scores decreased over time for those people with prediabetes (18.6% in year 1 vs. 15.9% in year 10, P < 0.01). The lower score in the diabetes group versus other groups, a declining score in the prediabetes group, and favorable changes in each individual risk factor in all groups were explained, in part, by higher or increasing medication use for lipids and blood pressure. CONCLUSIONS Prediabetes represents a high-risk state for CVD. Restoration of NGR and/or medical treatment of CVD risk factors can significantly reduce the estimated CVD risk in people with prediabetes.

Delayed Gastric Emptying is Associated with Early and Long-Term Hyperglycemia in Type 1 Diabetes Mellitus

BACKGROUND & AIMS After the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study continued to show persistent benefit of prior intensive therapy on neuropathy, retinopathy, and nephropathy in type 1 diabetes mellitus (DM). The relationship between control of glycemia and gastric emptying (GE) is unclear. METHODS We assessed GE with a (13)C-spirulina breath test and symptoms in 78 participants with type 1 diabetes at year 20 of EDIC. The relationship between delayed GE and glycated hemoglobin (HbA1c), complications of DM, and gastrointestinal symptoms were evaluated. RESULTS GE was normal (37 participants; 50%), delayed (35 participants; 47%), or rapid (2 participants; 3%). The latest mean HbA1c was 7.7%. In univariate analyses, delayed GE was associated with greater DCCT baseline HbA1c and duration of DM before DCCT (P ≤ .04), greater mean HbA1c over an average of 27 years of follow-up evaluation (during DCCT-EDIC, P = .01), lower R-R variability during deep breathing (P = .03) and severe nephropathy (P = .05), and a greater composite upper gastrointestinal symptom score (P < .05). In multivariate models, retinopathy was the only complication of DM associated with delayed GE. Separately, DCCT baseline HbA1c (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.3) and duration of DM (OR, 1.2; 95% CI, 1.01-1.3) before DCCT entry and mean HbA1c during DCCT-EDIC (OR, 2.2; 95% CI, 1.04-4.5) were associated independently with delayed GE. CONCLUSIONS In the DCCT/EDIC study, delayed GE was remarkably common and associated with gastrointestinal symptoms and with measures of early and long-term hyperglycemia. ClinicalTrials.gov numbers NCT00360815 and NCT00360893.

Musculoskeletal Complications in Type 1 Diabetes

OBJECTIVE The development of periarticular thickening of skin on the hands and limited joint mobility (cheiroarthropathy) is associated with diabetes and can lead to significant disability. The objective of this study was to describe the prevalence of cheiroarthropathy in the well-characterized Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort and examine associated risk factors, microvascular complications, and the effect of former DCCT therapy (intensive [INT] vs. conventional [CONV]) on its development. RESEARCH DESIGN AND METHODS This cross-sectional analysis was performed in 1,217 participants (95% of the active cohort) in EDIC years 18/19 after an average of 24 years of follow-up. Cheiroarthropathy—defined as the presence of any one of the following: adhesive capsulitis, carpal tunnel syndrome, flexor tenosynovitis, Dupuytrens contracture, or a positive prayer sign—was assessed using a targeted medical history and standardized physical examination. A self-administered questionnaire (Disabilities of the Arm, Shoulder and Hand [DASH]) assessed functional disability. RESULTS Cheiroarthropathy was present in 66% of subjects (64% of the INT group and 68% of the CONV group; P = 0.1640) and was associated with age, sex, diabetes duration, skin intrinsic fluorescence, HbA1c, neuropathy, and retinopathy (P < 0.005 for each). DASH functional disability scores were worse among subjects with cheiroarthropathy (P < 0.0001). CONCLUSIONS Cheiroarthropathy is common in people with type 1 diabetes of long duration (∼30 years) and is related to longer duration and higher levels of glycemia. Clinicians should include cheiroarthropathy in their routine history and physical examination of patients with type 1 diabetes because it causes clinically significant functional disability.

Impact of inpatient diabetes management, education, and improved discharge transition on glycemic control 12 months after discharge

AIM To determine whether inpatient diabetes management and education with improved transition to outpatient care (IDMET) improves glycemic control after hospital discharge in patients with uncontrolled type 2 diabetes (T2DM). METHODS Adult inpatients with T2DM and HbA1c > 7.5% (58 mmol/mol) admitted for reasons other than diabetes to an academic medical center were randomly assigned to either IDMET or usual care (UC). Linear mixed models estimated treatment-dependent differences in the change in HbA1c (measured at 3, 6, and 12 months) from baseline to 1-year follow-up. RESULTS Thirty-one subjects had mean age 55 ± 12.6 years, with mean HbA1c of 9.7 ± 1.6% (82 ± 18 mmol/mol). Mean inpatient glucose was lower in the IDMET than in the UC group (176 ± 66 versus 195 ± 74 mg/dl [9.7 versus 10.8 mmol/l], P = 0.001). In the year after discharge, the average HbA1c reduction was greater in the IDMET group compared with the UC group by 0.6% (SE 0.5%, [7 (SE 5)mmol/mol], P = 0.3). Among patients newly discharged on insulin, the average HbA1c reduction was greater in the in the IDMET group than in the UC group by 2.4% (SE 1.0%, [25 (SE 11)mmol/mol], P = 0.04). CONCLUSIONS Inpatient diabetes management (IDMET) substantially improved glycemic control 1 year after discharge in patients newly discharged on insulin; patients previously treated with insulin did not benefit.

Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study

TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) is a federally funded multicenter randomized clinical trial comparing three treatments of youth onset type 2 diabetes.