bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Glucagon-Like Peptide 1 on Non–Insulin-Mediated Glucose Uptake in the Elderly Patient With Diabetes
Authors: Meneilly Graydon S. , McIntosh Christopher H.S. , Pederson Raymond A. , Habener Joel F. , Gingerich Ronald , Egan Josephine M. , Finegood Diane T. , Elahi Dariush
Published: March 2007

An important cause of elevated glucose levels in elderly patients with diabetes is an alteration in non–insulin-mediated glucose uptake (NIMGU). Glucagon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIMGU. This study was conducted to determine whether GLP-1 augments NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impaired. Studies were conducted on 10 elderly patients with type 2 diabetes (aged 75 ± 2 years, BMI 27 ± 1 kg/m2) who underwent paired 240-min glucose clamp studies. In each study, octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose was infused. From 180 to 240 min, glucose was increased to 11 mmol/l using the glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control study, insulin was infused using the glucose clamp protocol from 30 to 240 min to match the insulin levels that occurred during the GLP-1 infusion study. During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 ± 0.19 mg · kg–1 · min–1; GLP-1 study: 2.90 ± 0.17 mg · kg–1 · min–1; P < 0.0001). Hepatic glucose output was not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes.
Effects of Sibutramine in Obese Female Subjects With Type 2 Diabetes and Poor Blood Glucose Control
Authors: Gokcel Adnan , Karakose Hatice , Ertorer Eda Melek , Tanaci Nedret , Tutuncu Neslihan Bascil , Guvener Nilgun
Published: March 2007

OBJECTIVE—In this study, we evaluated the efficacy of sibutramine in combination with hypoglycemic drugs in obese type 2 diabetic women whose glucose levels were poorly regulated.

RESEARCH DESIGN AND METHODS—Female patients with type 2 diabetes, poorly controlled glucose levels, and HbA1c >8% were randomly assigned to one of two groups. In addition to their prescribed hypoglycemic agents (maximum doses of sulfonylureas and metformin), one group (n = 30) received a placebo twice daily for 6 months and the other (n = 30) received sibutramine 10 mg b.i.d. for the same period.

RESULTS—One patient in the sibutramine group was excluded during the study period because of hypertension; thus, a total of 29 data sets were analyzed for this group. In the placebo group, five patients had to be excluded because of low treatment efficacy, leaving a total of 25 who completed the study. Comparing the changes that occurred over 6 months in the sibutramine and placebo groups, the former showed significantly greater reductions in fasting blood glucose (P < 0.0001), second-hour postprandial blood glucose (P < 0.0001), insulin resistance (P < 0.0001), waist circumference (P < 0.0001), BMI (P < 0.0001), HbA1c (P < 0.0001), diastolic blood pressure, pulse rate, uric acid levels, and all elements of the lipid profile except HDL cholesterol and apolipoprotein A1.

CONCLUSIONS—The addition of sibutramine to oral hypoglycemic therapy resulted in significant weight loss and improvement in metabolic parameters in this patient group. Sibutramine is an effective adjunct to oral hypoglycemic therapy in obese women with type 2 diabetes.
Reduced Cardiovascular Morbidity and Mortality in Hypertensive Diabetic Patients on First-Line Therapy With an ACE Inhibitor Compared With a Diuretic/β-Blocker–Based Treatment Regimen
Authors: Niskanen Leo , Hedner Thomas , Hansson Lennart , Lanke Jan , Niklason Anders ,   for the CAPPP study group
Published: March 2007

OBJECTIVE—The Captopril Prevention Project (CAPPP) evaluated the effects of an ACE inhibitor–based therapeutic regimen on cardiovascular mortality and morbidity in hypertension. One planned subanalysis of the CAPPP was to evaluate the outcome in the diabetic patient group.

RESEARCH DESIGN AND METHODS—In the CAPPP, 572 (4.9% of 10,985 hypertensive patients) had diabetes at baseline and were studied according to a prospective, randomized, open, blinded, end point trial design. Patients aged 25–66 years with diastolic blood pressure ≥100 mmHg were included and randomized to receive either captopril or conventional antihypertensive treatment (diuretics and/or β-blockers).

RESULTS—The primary end point, fatal and nonfatal myocardial infarction and stroke as well as other cardiovascular deaths, was markedly lower in the captopril than in the conventional therapy group (relative risk [RR] = 0.59; P = 0.018). Specifically, cardiovascular mortality, defined as fatal stroke and myocardial infarction, sudden death, and other cardiovascular death, tended to be lower in the captopril group (RR = 0.48; P = 0.084), and no difference was observed between the study groups for stroke (RR = 1.02; P = 0.96). Myocardial infarctions were less frequent in the captopril group than in the conventional therapy group (RR = 0.34; P = 0.002). Furthermore, total mortality was lower in the captopril as compared with the conventional therapy group (RR = 0.54; P = 0.034). Patients with impaired metabolic control seemed to benefit the most from ACE inhibitor–based therapy.

CONCLUSIONS—Captopril is superior to a diuretic/β-blocker antihypertensive treatment regimen in preventing cardiovascular events in hypertensive diabetic patients, especially in those with metabolic decompensation.
Rapid Progression of Albumin Excretion Is an Independent Predictor of Cardiovascular Mortality in Patients With Type 2 Diabetes and Microalbuminuria
Authors: Spoelstra-de Man Angélique M.E. , Brouwer Catherine B. , Stehouwer Coen D.A. , Smulders Yvo M.
Published: March 2007

OBJECTIVE—In patients with type 2 diabetes, microalbuminuria is associated with an increase in predominantly cardiovascular mortality. Considerable interindividual variability in the rate of progression of microalbuminuria exists. The prognostic significance of rate of progression of microalbuminuria with regard to cardiovascular and renal clinical end points is, however, unknown. The purpose of this study was to determine the prognostic significance of rate of progression of microalbuminuria for cardiovascular end points and renal function.

RESEARCH DESIGN AND METHODS—In a previous prospective cohort study, progression of microalbuminuria (expressed as mean yearly change in albumin-to-creatinine ratio) was assessed in 58 patients with type 2 diabetes. During a median follow-up of 7 years after progression of microalbuminuria was determined, we registered all-cause mortality and coronary heart disease mortality as primary end points and coronary heart disease (fatal or nonfatal), peripheral vascular disease, ischemic stroke, retinopathy, macroalbuminuria, and change in serum creatinine as secondary end points.

RESULTS—Seven subjects died during the study; five of these subjects died of coronary heart disease. Cox’s regression analysis identified progression of microalbuminuria as a significant predictor of all-cause mortality (hazard ratio 1.46 per point increase in albumin-to-creatinine ratio per year, P < 0.001), coronary heart disease mortality (hazard ratio 2.32, P = 0.006), and macroalbuminuria (hazard ratio 1.79, P < 0.001). Adjustment for multiple cardiovascular risk factors did not affect these results. Identical analyses for baseline level of microalbuminuria instead of progression rate of microalbuminuria did not show significant hazard ratios. In addition, progression of microalbuminuria significantly predicted an increase in serum creatinine (r = 0.29, P = 0.04).

CONCLUSIONS—In patients with type 2 diabetes and microalbuminuria, the rate of progression of albumin excretion seems to be a powerful independent predictor of mortality caused mainly by coronary heart disease.
A Foot Care Program for Diabetic Unilateral Lower-Limb Amputees
Authors: Carrington Anne L. , Abbott Caroline A. , Griffiths Joan , Jackson Nicky , Johnson Sylvia R. , Kulkarni Jai , Van Ross Ernest R.E. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE— To assess the efficacy of a specialist foot care program designed to prevent a second amputation and to assess peripheral vascular disease (PVD) and peripheral neuropathy in diabetic unilateral lower-limb amputees.

RESEARCH DESIGN AND METHODS— Investigations were carried out in 143 diabetic lower-limb unilateral amputees referred to a subregional rehabilitation center for prosthetic care from a catchment area of ∼3 million people. Peripheral vascular and nerve assessment, education, and podiatry were provided for each patient.

RESULTS— For the patients referred to the foot care program,there were no baseline differences between the patients who proceeded to a bilateral amputation (n = 22) and those who remained as unilateral amputees (n = 121) in their level of foot care knowledge and mean neuropathy scores. Mean ankle-brachial pressure index was significantly lower for the bilateral amputees (0.75 ± 0.04) compared with the unilateral amputees (0.90 ± 0.03, mean ± SEM, P < 0.05), but there was no difference in the level of oxygen in the skin. However, the level of carbon dioxide was significantly lower in patients with bilateral amputation (24.21 ± 2.16 vs. 31.20 ± 0.85 mmHg, P <0.03). Overall, the establishment of a specialist foot care program made no impact on contralateral limb amputation (22 of 143, 15.4%) compared with matched patients without the program (21 of 148, 14%) over a 2-year outcome period for each patient.

CONCLUSIONS— PVD is more closely associated with diabetic bilateral amputation than neuropathy or level of foot care knowledge. Preventative foot care programs for diabetic unilateral amputees should therefore place greater emphasis on peripheral vascular assessment to identify patients at risk and on the development of timely intervention strategies.
Factors Influencing Glycemic Control in Young People With Type 1 Diabetes in Scotland
Authors:   Scottish Study Group for the Care of the Young Diabetic
Published: March 2007

OBJECTIVE— To evaluate differences in HbAlcconcentrations between centers and to assess the factors associated with glycemic control in young people with type 1 diabetes in Scotland.

RESEARCH DESIGN AND METHODS— Data on 1,755 patients (94% of those registered) were collected from 18 centers providing care to children<15 years of age. At every clinic visit, a duplicate HbAlcsample was measured in a reference laboratory, and clinical information was collected prospectively.

RESULTS— Average HbAlc concentration was 9.1%(range 5.0-15.0). The following significant associations with HbAlclevel were identified: age, insulin regimen, BMI, season, social circumstances, and family history. HbAlc concentrations were significantly worse in older children (age 10-15 years 9.5% vs. other ages 8.8%, P < 0.001), those using two injections per day (2/day 9.1%vs. 3/day 8.8%, P < 0.01), children without both parents at home(9.4 vs. 9.0%, P < 0.001), a sibling with diabetes (9.7% vs. no family history 9.1%, P < 0.001). HbAlc concentration ranged from 8.1 to 10.2% between centers, after adjustment for factors associated with poor HbAlc (P < 0.001).

CONCLUSIONS— The overall glycemic control of diabetic young people in Scotland is equivalent to a Diabetes Control and Complications Trial HbAlc concentration of 8.7%, placing the majority at a high risk of the complications of diabetes in adulthood. Although factors were significantly associated with poor HbAlc, adjustment for these did not explain the differences between centers. We suggest that factors not analyzed in DIABAUD2 (e.g., deployment of resources, organization of the clinical structure, strategies of care, and clinic philosophy) are the determinants of HbAlc. We speculate that the style of utilization of optimum resources is the key to achieving good glycemic control.
Comparison of the Soluble Basal Insulin Analog Insulin Detemir With NPH Insulin
Authors: Hermansen Kjeld , Madsbad Sten , Perrild Hans , Kristensen Allan , Axelsen Mads
Published: March 2007

OBJECTIVE— Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose—lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia,dose requirements, and safety.

RESEARCH DESIGN AND METHODS— This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin.

RESULTS— The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%)(P = 0.049).

CONCLUSIONS— Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.
Relationship Between Plasma Sialic Acid Concentration and Microvascular and Macrovascular Complications in Type 1 Diabetes
Authors: Crook Martin A. , Pickup John C. , Lumb Peter J. , Georgino Francesco , Webb David J. , Fuller John H. ,   The EURODIAB IDDM Complications Study Group
Published: March 2007

OBJECTIVE— To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes.

RESEARCH DESIGN AND METHODS— We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy,neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries.

RESULTS— There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P <0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration,HbAlc, plasma triglyceride and cholesterol concentrations,waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men.

CONCLUSIONS— We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.
Contribution of Nerve-Axon Reflex-Related Vasodilation to the Total Skin Vasodilation in Diabetic Patients With and Without Neuropathy
Authors: Hamdy Osama , Abou-Elenin Karim , LoGerfo Frank W. , Horton Edward S. , Veves Aristidis
Published: March 2007

OBJECTIVE— To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects.

RESEARCH DESIGN AND METHODS— The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water.

RESULTS— The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside,which does not specifically stimulate the C nociceptive fibers.

CONCLUSIONS— Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.
Renal Gluconeogenesis
Authors: Gerich John E. , Meyer Christian , Woerle Hans J. , Stumvoll Michael
Published: March 2007

Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently, however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.
Racial and Ethnic Differences in Health Care Access and Health Outcomes for Adults With Type 2 Diabetes
Authors: Harris Maureen I.
Published: March 2007

OBJECTIVE—To evaluate health care access and utilization and health status and outcomes for type 2 diabetic patients according to race and ethnicity and to determine whether health status is influenced by health care access and utilization.

RESEARCH DESIGN AND METHODS—National samples of Caucasians, African-Americans, and Mexican-Americans were studied in the third National Health and Nutrition Examination Survey. Information on medical history and treatment of diabetes, health care access and utilization, and health status and outcomes was obtained by structured questionnaires and by clinical and laboratory assessments.

RESULTS—Almost all patients in each race and ethnic group had one primary source of ambulatory medical care (92–97%), saw one physician at this source (83–92%), and had at least semiannual physician visits (83–90%). Almost all patients ≥65 years of age had health insurance (99–100%), and for those patients <65 years of age, Caucasians (91%) and African-Americans (89%) had higher rates of coverage than Mexican-Americans (66%). Rates of treatment with insulin or oral agents (71–78%), eye examination in the previous year (61–70%), blood pressure check in the previous 6 months (83–89%), and the proportion of hypertension that was diagnosed (84–91%) were similar for each race and ethnic group. Lower proportions of African-Americans and Mexican-Americans self-monitored their blood glucose (insulin-treated, 27 vs. 44% of Caucasians), had their cholesterol checked (62–68 vs. 81%), and had their dyslipidemia diagnosed (45 vs. 58%). African-American and Mexican-American patients had a somewhat higher proportion than Caucasian patients, with HbA1c ≥7% (58–66 vs. 55%), blood pressure ≥140/90 mmHg among those with diagnosed hypertension (60–65 vs. 55%), and clinical proteinuria (11–14 vs. 5%). In contrast, they had better levels of total cholesterol (≥240 mg/dl) (28–30 vs. 34%) and HDL cholesterol (≥45 mg/dl) (46–59 vs. 38%), and African-American and Mexican-American men were less overweight than Caucasian men (BMI ≥30) (34–37 vs. 44%), although the opposite was true for women. LDL cholesterol levels and the proportion of patients who smoked cigarettes or were hospitalized in the past year were similar among all three groups. In logistic regression analysis, there was little evidence that levels of blood glucose, blood pressure, lipids, or albuminuria were associated with access to or utilization of health care or with socioeconomic status.

CONCLUSIONS—There are some differences by race and ethnicity in health care access and utilization and in health status and outcomes for adults with type 2 diabetes. However, the magnitude of these differences pale in comparison with the suboptimal health status of all three race and ethnic groups relative to established treatment goals. Health status does not appear to be influenced by access to health care.
Diagnosing Insulin Resistance in the General Population
Authors: McAuley Kirsten A. , Williams Sheila M. , Mann Jim I. , Walker Robert J. , Lewis-Barned Nick J. , Temple Lara A. , Duncan Ashley W.
Published: March 2007

OBJECTIVE—Difficulties in measuring insulin sensitivity prevent the identification of insulin-resistant individuals in the general population. Therefore, we compared fasting insulin, homeostasis model assessment (HOMA), insulin-to-glucose ratio, Bennett index, and a score based on weighted combinations of fasting insulin, BMI, and fasting triglycerides with the euglycemic insulin clamp to determine the most appropriate method for assessing insulin resistance in the general population.

RESEARCH DESIGN AND METHODS—Family history of diabetes, BMI, blood pressure, waist and hip circumference, fasting lipids, glucose, insulin, liver enzymes, and insulin sensitivity index (ISI) using the euglycemic insulin clamp were obtained for 178 normoglycemic individuals aged 25–68 years. Product-moment correlations were used to examine the association between ISI and various surrogate measurements of insulin sensitivity. Regression models were used to devise weights for each variable and to identify cutoff points for individual components of the score. A bootstrap procedure was used to identify the most useful predictors of ISI.

RESULTS—Correlation coefficients between ISI and fasting insulin, HOMA, insulin-to-glucose ratio, and the Bennett index were similar in magnitude. The variables that best predicted insulin sensitivity were fasting insulin and fasting triglycerides. The use of a score based on \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[Mffm{/}I{\,}{\,}{=}{\,}{\,}exp{[}2.63{\,}{\,}{-}{\,}{\,}0.28ln(insulin){\,}{\,}{-}{\,}{\,}0.31ln(TAG){]}\] \end{document}rather than the use of fasting insulin alone resulted in a higher sensitivity and a maintained specificity when predicting insulin sensitivity.

CONCLUSIONS—A weighted combination of two routine laboratory measurements, i.e., fasting insulin and triglycerides, provides a simple means of screening for insulin resistance in the general population.
Anemia With Erythropoietin Deficiency Occurs Early in Diabetic Nephropathy
Authors: Bosman Deborah R. , Winkler Andrea S. , Marsden Joanne T. , Macdougall Iain C. , Watkins Peter J.
Published: March 2007

OBJECTIVE—The normochromic normocytic anemia of erythropoietin (EPO) deficiency is recognized in advanced renal failure but not in early renal disease. The aim of this study was to determine whether anemia with EPO deficiency is found in type 1 diabetic patients with diabetic nephropathy in the absence of advanced renal failure and to compare them with patients with nondiabetic renal disease of similar severity.

RESEARCH DESIGN AND METHODS—A total of 27 type 1 diabetic patients with diabetic nephropathy (DN), defined as having persistent proteinuria (mean 1,086 mg/day [CI 120–5,190]), a serum creatinine ≤180 μmol/l, and retinopathy, were compared with 26 nondiabetic patients with glomerulonephritis (GN) and persistent proteinuria (1,874 mg/day [349–5,005]). The Hb concentration, red cell indexes, and serum EPO levels were measured, and other causes for the anemia were excluded. The EPO values were compared with a normal reference range obtained from nondiabetic patients with a microcytic anemia. The DN patients were tested for signs of diabetic peripheral and autonomic neuropathy.

RESULTS—We found that 13 of the 27 DN patients were anemic (Hb 10.6 ± 0.9 g/dl) in marked contrast to none of the GN patients (Hb 13.7 ± 1.4 g/dl, P < 0.005). In the DN group, serum EPO concentrations failed to increase in response to anemia compared with the response seen in patients with microcytic anemia. Thus, the anemia of the DN group was associated with EPO deficiency. The anemic DN patients showed evidence of more severe proteinuria and diabetic neuropathy than the nonanemic DN patients.

CONCLUSIONS—Anemia associated with EPO deficiency can occur early in DN before the onset of advanced renal failure, but does not normally occur in nondiabetic renal disease of similar severity. The pathogenesis requires elucidation.
Effectiveness of Self-Management Training in Type 2 Diabetes
Authors: Norris Susan L. , Engelgau Michael M. , Venkat Narayan K.M.
Published: March 2007

OBJECTIVE—To systematically review the effectiveness of self-management training in type 2 diabetes.

RESEARCH DESIGN AND METHODS—MEDLINE, Educational Resources Information Center (ERIC), and Nursing and Allied Health databases were searched for English-language articles published between 1980 and 1999. Studies were original articles reporting the results of randomized controlled trials of the effectiveness of self-management training in people with type 2 diabetes. Relevant data on study design, population demographics, interventions, outcomes, methodological quality, and external validity were tabulated. Interventions were categorized based on educational focus (information, lifestyle behaviors, mechanical skills, and coping skills), and outcomes were classified as knowledge, attitudes, and self-care skills; lifestyle behaviors, psychological outcomes, and quality of life; glycemic control; cardiovascular disease risk factors; and economic measures and health service utilization.

RESULTS—A total of 72 studies described in 84 articles were identified for this review. Positive effects of self-management training on knowledge, frequency and accuracy of self-monitoring of blood glucose, self-reported dietary habits, and glycemic control were demonstrated in studies with short follow-up (<6 months). Effects of interventions on lipids, physical activity, weight, and blood pressure were variable. With longer follow-up, interventions that used regular reinforcement throughout follow-up were sometimes effective in improving glycemic control. Educational interventions that involved patient collaboration may be more effective than didactic interventions in improving glycemic control, weight, and lipid profiles. No studies demonstrated the effectiveness of self-management training on cardiovascular disease–related events or mortality; no economic analyses included indirect costs; few studies examined health-care utilization. Performance, selection, attrition, and detection bias were common in studies reviewed, and external generalizability was often limited.

CONCLUSIONS—Evidence supports the effectiveness of self-management training in type 2 diabetes, particularly in the short term. Further research is needed to assess the effectiveness of self-management interventions on sustained glycemic control, cardiovascular disease risk factors, and ultimately, microvascular and cardiovascular disease and quality of life.
Long-Term (5-Year) Effects of a Reduced-Fat Diet Intervention in Individuals With Glucose Intolerance
Authors: Swinburn Boyd A. , Metcalf Patricia A. , Ley Sarah J.
Published: March 2007

OBJECTIVE—To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance.

RESEARCH DESIGN AND METHODS—A 5-year follow-up of a 1-year randomized controlled trial of a reduced-fat ad libitum diet versus a usual diet. Participants with glucose intolerance (2-h blood glucose 7.0–11.0 mmol/l) were recruited from a Workforce Diabetes Survey. The group that was randomized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline, 6 months, and 1 year (end of intervention), with follow-up at 2 years (n = 104), 3 years (n = 99), and 5 years (n = 103).

RESULTS—Compared with the control group, weight decreased in the reduced-fat–diet group (P < 0.0001); the greatest difference was noted at 1 year (–3.3 kg), diminished at subsequent follow-up (−3.2 kg at 2 years and −1.6 kg at 3 years), and was no longer present by 5 years (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47 vs. 67%, P < 0.05), but in subsequent years, there were no differences between groups. However, the more compliant 50% of the intervention group maintained lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026, respectively) compared with control subjects.

CONCLUSIONS—The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake.
Guidelines for Premeal Insulin Dose Reduction for Postprandial Exercise of Different Intensities and Durations in Type 1 Diabetic Subjects Treated Intensively With a Basal-Bolus Insulin Regimen (Ultralente-Lispro)
Authors: Rabasa-Lhoret Rémi , Bourque Josée , Ducros Francine , Chiasson Jean-Louis
Published: March 2007

OBJECTIVE—To evaluate and validate appropriate premeal insulin dose reductions for postprandial exercises of different intensities and durations to minimize the risk of exercise-induced hypoglycemia in type 1 diabetic subjects.

RESEARCH DESIGN AND METHODS—Eight male type 1 diabetic patients on a basal-bolus insulin regimen of ultralente (UL) as basal insulin and lispro (LP) as premeal insulin were tested in a randomized, crossover fashion during postprandial exercise at 25% Vo2max for 60 min, 50% Vo2max for 30 and 60 min, and 75% Vo2max for 30 min starting 90 min after a standardized mixed breakfast (600 kcal, 75 g carbohydrates). Each subject served as his own control and was tested after a full dose of insulin LP (LP 100%) and/or 50% (LP 50%) and/or 25% (LP 25%) of the current dose.

RESULTS—At all intensities, the full premeal insulin dose was associated with an increased risk of hypoglycemia. At 25% Vo2max for 60 min, a 50% reduction in the premeal insulin dose resulted in plasma glucose of −0.62 mmol/l compared with baseline at the end of exercise. At 50% Vo2max for 30 and 60 min, 50 and 75% reductions of the premeal insulin dose were associated with plasma glucose of −0.39 and +0.49 mmol/l, respectively, at the end of the exercise. At 75% Vo2max, a 75% reduction of the premeal insulin dose was required to achieve appropriate postexercise plasma glucose (+0.71 mmol/l). Such reductions in the premeal insulin dose resulted in a 75% decrease in the incidence of exercise-induced hypoglycemia.

CONCLUSIONS—In well-controlled type 1 diabetic subjects on intensive insulin therapy with the basal-bolus (UL-LP) insulin regimen, risk of hypoglycemia can be minimized during postprandial exercises of different intensities and different durations by appropriate reduction of premeal insulin LP.
Basal Insulin Therapy in Type 2 Diabetes
Authors: Rosenstock Julio , Schwartz Sherwyn L. , Clark Charles M. , Park Glen D. , Donley David W. , Edwards Mike B.
Published: March 2007

OBJECTIVE—To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone.

RESEARCH DESIGN AND METHODS—A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily (n = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose <6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg.

RESULTS—The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means ± SD) in HbA1c from baseline to end point was similar in the insulin glargine group (−0.41 ± 0.1%) and the NPH group (−0.59 ± 0.1%) after patients began with an average baseline HbA1c of ∼8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.8%). However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase (26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P < 0.0007).

CONCLUSIONS—In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine demonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.
Blood Glucose Awareness Training (BGAT-2)
Authors: Cox Daniel J. , Gonder-Frederick Linda , Polonsky William , Schlundt David , Kovatchev Boris , Clarke William
Published: March 2007

OBJECTIVE—Blood glucose awareness training (BGAT) has been shown to improve awareness of blood glucose (BG) fluctuations among adults with type 1 diabetes. This study investigates the long-term (12-month) benefits of BGAT-2.

RESEARCH DESIGN AND METHODS—A total of 73 adults with type 1 diabetes participated in a 6-month repeated baseline design with a 12-month follow-up. At 6 months and 1 month before BGAT-2 and at 1, 6, and 12 months after BGAT-2, subjects used a handheld computer for 50 trials and completed psychological tests. Throughout assessment, subjects completed diaries, recording occurrences of diabetic ketoacidosis, severe hypoglycemia, and motor vehicle violations. During follow-up, 50% of the subjects received booster training.

RESULTS—During the first and last halves of both the baseline period and the follow-up period, dependent variables were generally stable. However, from baseline to follow-up, BGAT-2 led to 1) improved detection of hypoglycemia and hyperglycemia; 2) improved judgment regarding when to lower high BG, raise low BG, and not drive while hypoglycemic; 3) reduction in occurrence of diabetic ketoacidosis, severe hypoglycemia, and motor vehicle violations; and 4) improvement in terms of worry about hypoglycemia, quality of life, and diabetes knowledge. Reduction in severe hypoglycemia was not associated with a worsening of metabolic control (HbA1). The presence or absence of booster training did not differentially affect these benefits.

CONCLUSION—BGAT has sustained broad-ranging benefits, independent of booster intervention.
Mini-Dose Glucagon Rescue for Hypoglycemia in Children With Type 1 Diabetes
Authors: Haymond Morey W. , Schreiner Barbara
Published: March 2007

OBJECTIVE—Children with type 1 diabetes are frequently difficult to manage during times of gastroenteritis or poor oral intake of carbohydrates because of mild or impending hypoglycemia. The present study describes the effective use of small doses of subcutaneous glucagon in these children.

RESEARCH DESIGN AND METHODS—We analyzed 33 episodes of impending or mild hypoglycemia in 28 children (ages 6.6 ± 0.7 years). All were healthy except for type 1 diabetes and an episode of gastroenteritis. Using a standard U-100 insulin syringe, children ages ≤2 years received two “units” (20 μg) of glucagon subcutaneously and those ages >2 years received one unit/year of age up to 15 units (150 μg). If the blood glucose did not increase within 30 min, the initial dosage was doubled and given at that time. We used patients’ self-glucose monitoring devices, aqueous glucagon, standard insulin syringes, and frequent phone contact with a physician and/or a diabetes nurse educator in this study.

RESULTS—Blood glucose was 3.44 ± 0.15 mmol/l before and 8.11 ± 0.72 mmol/l 30 min after glucagon. In 14 children, relative hypoglycemia recurred, requiring retreatment (3.48 ± 0.18 to 6.94 ± 0.72 mmol/l). In four children, a third dose was required. The glucagon was well tolerated. In 28 of the 33 episodes of impending hypoglycemia, the children remained at home and fully recovered. Five children were taken to their local hospital because of concerns of dehydration or fever, but none for hypoglycemia.

CONCLUSIONS—Mini-dose glucagon rescue, using subcutaneous injections, is effective in managing children with type 1 diabetes during episodes of impending hypoglycemia due to gastroenteritis or poor oral intake of carbohydrate.
Type 1 Diabetes Environmental Factors and Correspondence Analysis of HLA Class II Genes in the Yemenite Jewish Community in Israel
Authors: Weintrob Naomi , Sprecher Elliot , Israel Shoshana , Pinhas-Hamiel Orit , Kwon Oh Joong , Bloch Konstantin , Abramov Natali , Arbel Aviva , Josefsberg Zeev , Brautbar Chaim , Vardi Pnina
Published: March 2007

OBJECTIVE—The Israeli Yemenite Jewish community has displayed an exceptionally rapid increase in the frequency of type 1 diabetes, having the highest rate of all Israeli ethnic groups. We studied the role of the environment, in relation to the nature and frequency of HLA class II genes, to evaluate its possible involvement in the development of diabetes.

RESEARCH DESIGN AND METHODS—We interviewed 196 elderly Yemenite women, who had immigrated to Israel as adults, in programmed encounters about signs and symptoms of type 1 diabetes, infant feeding customs, and infectious diseases in Yemen. We also performed HLA oligotyping of DRB1, DQA1, and DQB1 genes in 120 unrelated Yemenite Jews, including 44 type 1 diabetic patients and 76 healthy control subjects, and used these data in correspondence analysis comparing Yemenites with different Israeli ethnic groups.

RESULTS—Interviews indicated that early exposure to cow’s milk was very common in Yemen. However, none of the women could recall classical presentations of diabetes. HLA oligotyping showed that gene frequencies of non-Asp-57 (of the HLA-DQB chain) in the patients (0.94) and control subjects (0.6) were similar to those of other populations with a known high incidence of type 1 diabetes. Correspondence analysis revealed that Yemenite Jews are genetically distinct from other ethnic groups in Israel.

CONCLUSIONS—The genetic distinctiveness of Yemenite Jews may explain their unusually high incidence of type 1 diabetes in Israel. Despite the presence of highly susceptible diabetogenic HLA class II genes in this community, early exposure to cow’s milk did not cause phenotypic expression of diabetes in Yemen. This finding suggests that in this population, either cow’s milk does not play a crucial role in triggering diabetes, or environmentally conferred protection, such as frequent infectious disease in Yemen, was dominant.
Disordered Eating, Body Mass, and Glycemic Control in Adolescents With Type 1 Diabetes
Authors: Meltzer Lisa J. , Johnson Suzanne Bennett , Prine Jason M. , Banks Richard A. , Desrosiers Paul M. , Silverstein Janet H.
Published: March 2007

OBJECTIVE—To examine the relationship between disordered eating attitudes and behaviors, BMI, and glycemic control in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—In a cross-sectional design, 152 adolescents (ages 11–19 years) completed three scales from the Eating Disorders Inventory (EDI): Body Dissatisfaction, Drive for Thinness, and Bulimia. All subjects had diabetes for >1 year. Glycemic control was assessed by glycosylated hemoglobin (HbA1c). Height and weight were measured to assess BMI.

RESULTS—Adolescents with type 1 diabetes did not report more disordered eating attitudes and behaviors than the normative comparison sample. Male subjects with type 1 diabetes reported fewer symptoms of bulimia and female subjects with type 1 diabetes reported greater body satisfaction than the normative group. A higher BMI was a significant predictor of greater body dissatisfaction, more so for female than male subjects. Symptoms of bulimia were associated with older adolescence and female sex. Those with more symptoms of bulimia were also more likely to have a higher BMI. Sex (female) and body dissatisfaction (more dissatisfied) predicted a stronger desire to be thin. Longer duration of disease, more symptoms of bulimia, and obesity all predicted poorer glycemic control.

CONCLUSIONS—Female patients aged 13–14 years seem to be at greatest risk for developing disordered eating patterns. Using the clinical cutoff score (≥5) of the EDI Bulimia subscale as a screener in diabetes clinics may help identify adolescents whose disordered eating patterns are likely to compromise their glycemic control.
The Effect of Indian or Anglo Dietary Preference on the Incidence of Diabetes in Pima Indians
Authors: Williams Desmond E. , Knowler William C. , Smith Cynthia J. , Hanson Robert L. , Roumain Janine , Saremi Aramesh , Kriska Andrea M. , Bennett Peter H. , Nelson Robert G.
Published: March 2007

OBJECTIVE—In short-term studies, adoption of a traditional diet is associated with reduction in metabolic abnormalities often found in populations experiencing rapid lifestyle changes. We examined the long-term effects of a self-assessed traditional or nontraditional dietary pattern on the development of type 2 diabetes in 165 nondiabetic Pima Indians.

RESEARCH DESIGN AND METHODS—Dietary intake was assessed in 1988 by a quantitative food frequency method, and subjects were asked to classify their diet as “Indian,” “Anglo,” or “mixed.” The Indian diet reflects a preference for Sonoran-style and traditional desert foods. The Anglo diet reflects a preference for non-Sonoran–style foods typical of the remaining regions of the U.S.

RESULTS—In women, the intake of complex carbohydrates, dietary fiber, insoluble fiber, vegetable proteins, and the proportion of total calories from complex carbohydrate and vegetable proteins were significantly higher (P < 0.05) in the Indian than in the Anglo diet. The mixed diet was intermediate in of all these constituents. In men, the intake for these nutrients was also higher in the Indian than in the Anglo group, but not significantly. Diabetes developed in 36 subjects (8 men and 28 women) during 6.2 years of follow-up (range 0.9–10.9). The crude incidence rates of diabetes were 23, 35, and 63 cases per 1,000 person-years in the Indian, mixed, and Anglo groups, respectively. After adjustment for age, sex, BMI, and total energy intake in a proportional hazards model, the risk of developing diabetes in the Anglo-diet group was 2.5 times as high (95% CI 0.9–7.2) and the rate in the mixed-diet group was 1.3 times as high (0.6–3.3) as in the Indian-diet group.

CONCLUSIONS—This study suggests that the adoption of an Anglo diet may increase the risk of developing diabetes in Pima Indians, but it does not provide unequivocal evidence for or against this hypothesis.
Mortality Trends in Type 1 Diabetes
Authors: Nishimura Rimei , LaPorte Ronald E. , Dorman Janice S. , Tajima Naoko , Becker Dorothy , Orchard Trevor J.
Published: March 2007

OBJECTIVES—To investigate long-term mortality and its temporal trends as of 1 January 1999 among the 1,075 patients with type 1 diabetes (onset age <18 years, diagnosed between 1965 and 1979) who comprise the Allegheny County population-based registry.

RESEARCH DESIGN AND METHODS—Overall, sex- and race-specific mortality rates per person-year of follow-up were determined. Standardized mortality ratios were also calculated. Survival analyses and Cox proportional hazard model were also used. Temporal trends were examined by dividing the cohort into three groups by year of diagnosis (1965–1969, 1970–1974, and 1975–1979).

RESULTS—Living status of 972 cases was ascertained as of January 1, 1999 (ascertainment rate 90.4%). The mean duration of diabetes was 25.2 ± 5.8 (SD) years. Overall, 170 deaths were observed. The crude mortality rate was 627 per 100,000 person-years (95% CI 532–728) and standardized mortality ratio was 519 (440–602). Life-analyses by the Kaplan-Meier method indicated cumulative survival rates of 98.0% at 10 years, 92.1% at 20 years, and 79.6% at 30 years duration of diabetes. There was a significant improvement in the survival rate between the cohort diagnosed during 1965–1969 and that diagnosed during 1975–1979 by the log-rank test (P = 0.03). Mortality was higher in African-Americans than in Caucasians, but there were no differences seen by sex. The improvement in recent years was seen in both ethnic groups and sexes.

CONCLUSIONS—An improvement in long-term survival was observed in the more recently diagnosed cohort. This improvement is consistent with the introduction of HbA1 testing, home blood glucose monitoring, and improved blood pressure therapy in the 1980s.
Unchanged Incidence of Lower-Limb Amputations in a German City, 1990–1998
Authors: Trautner Christoph , Haastert Burkhard , Spraul Maximilian , Giani Guido , Berger Michael
Published: March 2007

OBJECTIVE—A reduction of diabetes-related amputations by at least one-half within 5 years was declared a primary objective for Europe (St. Vincent Declaration, 1989). We collected data about incidence rates of amputations in one German city (Leverkusen, with a population of ∼160,000 inhabitants) between 1990 and 1998 to ascertain a potential change in rates of incidence.

RESEARCH DESIGN AND METHODS—From all three hospitals in Leverkusen, we obtained complete lists of lower-limb amputations. From each patient record, diabetic status was determined. Only the first observed amputation was counted for the analysis. We estimated incidence rates of amputations in the entire population, the diabetic population, and the nondiabetic population. To test for time trend, we fitted Poisson regression models, adjusting for age and sex.

RESULTS—During the defined period (the years 1990, 1991, and 1994–1998), 339 patients (all residents of Leverkusen) without previous amputations had nontraumatic lower-limb amputations. Of all subjects, 46% were female. Moreover, 76% of the subjects were known to have diabetes. Mean age was 71.3 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population, per 100,000 person-years) were as follows: 1990, 549; 1991, 356; 1994, 544; 1995, 386; 1996, 426; 1997, 433; and 1998, 463. The Poisson models showed no significant change of incident amputations over time in the diabetic population or in the nondiabetic population.

CONCLUSIONS—Beyond random variation, no change of incidence rates could be observed over the past 9 years. More specific interventions are needed to achieve a substantial reduction of diabetes-related amputations.