bluuebunny/crossref_metadata_2025 huggingface dataset:
The 10-year incidence of renal insufficiency in people with type 1 diabetes.
Authors: Klein R , Klein B E , Moss S E , Cruickshanks K J , Brazy P C
Published: March 2007

OBJECTIVE: To describe the 10-year decrease in estimated creatinine clearance and the incidence of renal insufficiency and end-stage renal disease in a cohort of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: A population-based cohort of individuals with younger-onset diabetes (diagnosed at < 30 years old and taking insulin) participated in an examination during 1984-1986 (n = 891), a 6-year follow-up examination during 1990-1992 (n = 765), and a 10-year follow-up examination during 1995-1996 (n = 634). Serum creatinine and risk factors were measured during standardized protocols at each examination. Estimated adjusted creatinine clearance was computed by a modification of the Cockroft-Gault formula. A clinically meaningful change was defined as a decrease in the estimated annual creatinine clearance of > or = 3 ml.min-1.1.73 m-2.year-1. Renal insufficiency was defined by the development of a serum creatinine of 2.0 mg/dl or greater after the 1984-1986 examination. RESULTS: The 10-year estimated incidence of an annual decrease in the creatinine clearance of > or = 3 ml.min-1.1.73 m-2 for the cohort was 52.5%, and the cumulative 10-year incidence of renal insufficiency and end-stage renal failure was 14.4%. In univariate analyses, incidence of a decrease in the estimated creatinine clearance of > or = 3 ml.min-1.1.73 m-2.year-1 and the incidence of renal insufficiency were both related to higher glycosylated hemoglobin; higher diastolic blood pressure; the presence of microalbuminuria and gross proteinuria; more severe retinopathy; and a history of loss of tactile sensation or temperature sensitivity at baseline. In logistic regression analysis, after adjusting for the presence of microalbuminuria and gross proteinuria at baseline, higher glycosylated hemoglobin and higher diastolic blood pressure were associated with decreasing estimated creatinine clearance. In logistic regression analyses, after adjusting for the presence of microalbuminuria and gross proteinuria at baseline, the incidence of renal insufficiency was independently associated with age, glycosylated hemoglobin, hypertension, and serum HDL cholesterol. CONCLUSIONS: These data suggest that a public health approach aimed at controlling glycemia, blood pressure, and serum lipids might result in reducing the rate of decline in renal function and development of renal insufficiency in people with type 1 diabetes.
Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study.
Authors: de Marco R , Locatelli F , Zoppini G , Verlato G , Bonora E , Muggeo M
Published: March 2007

OBJECTIVE: This population-based study, carried out in the framework of the Verona Diabetes Study, investigated mortality from specific causes in known type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 7,148 known type 2 diabetic patients (3,366 men and 3,782 women) was identified on 31 December 1986 and followed up for 5 years (1987-1991). Underlying causes of death were obtained from death certificates and were coded according to the International Classification of Diseases, Ninth Revision. Cause-specific death rates of diabetic subjects were compared with those of the inhabitants of Verona. By 31 December 1991, 1,550 diabetic subjects (744 men and 806 women) had died. RESULTS: The standardized mortality ratio (SMR) for all causes of death was 1.42 (95% CI 1.35-1.50). The highest SMRs were for the following specific causes: diabetes (SMR 4.47 [3.91-5.10]), gastrointestinal diseases (1.83 [1.50-2.21])--particularly liver cirrhosis (2.52 [1.96-3.20])--and cardiovascular diseases (1.34 [1.23-1.44]), particularly cerebrovascular (1.48 [1.25-1.73]) and ischemic heart diseases (1.41 [1.24-1.62]). A significantly higher than expected risk of mortality for cardiovascular causes was already present in the first 5 years after diagnosis and decreased with age. Type 2 diabetic patients treated with insulin had a higher risk of dying than those treated orally or by diet. CONCLUSIONS: The highest SMRs in the diabetic cohort were for diabetes and liver cirrhosis. The mortality risk for cardiovascular diseases, although significantly higher than expected, was much lower in Italian type 2 diabetic patients than that reported for American patients. The evidence of an early effect on mortality suggests that prevention, early diagnosis, and treatment should be improved.
A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients.
Authors: Damsbo P , Clauson P , Marbury T C , Windfeld K
Published: March 2007

OBJECTIVE: This study was designed to compare diurnal blood glucose excursions and the effects of accidental dietary noncompliance in type 2 diabetic patients who are well-controlled on either repaglinide or glyburide treatment. RESEARCH DESIGN AND METHODS: This single-center double-blind randomized study comprised type 2 diabetic patients whose mean fasting blood glucose value after repaglinide/glyburide titration and stabilization was in the range of 90-140 mg/dl. The study consisted of an initial screening day, a titration period of 3 weeks, a 1-week stabilization period, a study period, and an end-of-study day. During the 3-day study period, half the patients of each group received two meals on the first day and three meals on the next 2 days, and in the other half, this sequence was reversed. Repaglinide was administered preprandially with each meal, and glyburide was administered as recommended in current labeling, i.e., either one or two daily doses before breakfast and dinner, regardless of whether lunch had been omitted. The diurnal blood glucose excursions on a day in which three meals were eaten were compared between the two groups, and the minimum blood glucose concentration (BGmin) measurements were compared between lunch and dinner on days with three and two meals. RESULTS: Of the 83 randomized patients, 43 entered into the 3-day study period and completed the trial. The results showed no significant differences between the repaglinide and glyburide groups in average blood glucose excursions from fasting blood glucose (P = 0.44). The influence on the mean BGmin of omitting a meal differed significantly between the repaglinide and glyburide groups (P = 0.014). In the latter group, BGmin decreased from 77 to 61 mg/dl as a result of omitting lunch, whereas in the repaglinide group, BGmin was unchanged for the two-meal day (78 mg/dl) and the three-meal day (76 mg/dl). All hypoglycemic events (n = 6) occurred in the glyburide group on the two-meal day, in connection with omitting lunch. No hypoglycemic events were recorded in the repaglinide group. CONCLUSIONS: These results suggest that treatment with repaglinide in well-controlled type 2 diabetic patients who miss or delay a meal is superior to treatment with longer-acting sulfonylurea drugs (such as glyburide) with respect to the risk of hypoglycemic episodes.
Increased Na+/Li+ countertransport activity may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria.
Authors: Chiarelli F , Catino M , Tumini S , de Martino M , Mezzetti A , Verrotti A , Vanelli M
Published: March 2007

OBJECTIVE: To evaluate whether erythrocyte sodium-lithium countertransport (Na+/Li+ CT) activity may identify adolescents and young adults with childhood-onset of type 1 diabetes to be at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: In January 1989, Na+/Li+ CT was measured in 170 normoalbuminuric diabetic adolescents and young adults (age 12-23 years; onset of diabetes before age 18 years; duration of diabetes longer than 7 years). Participants were clinically examined at baseline and biennially thereafter. Na+/Li+ CT activity was measured every 2 years during the 8-year follow-up period. Na+/Li+ CT activity was measured also in parents of diabetic offspring. RESULTS: Over 8 years, 18 (10 male, 8 female) out of 170 patients (10.5%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased Na+/Li+ CT (using 300 mumol.1 erythrocytes-1.h-1 as the arbitrary cutoff point) (group 1) compared with those with normal Na+/Li+ CT at the beginning of the study (group 2) (18.98 vs. 3.29%, P < 0.01; sensitivity 96.7%; specificity 57.9%). Sex did not influence predictive value, sensitivity, or specificity. Na+/Li+ CT was not significantly correlated with HbA1c or duration of type 1 diabetes. The percentage of offspring with both parents having Na+/Li+ CT activity above the median values was significantly higher in patients in group 1 than in group 2. The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate [AER], sex, HbA1c, mean blood pressure, cholesterol, triglycerides) in type 1 diabetic adolescents with elevated baseline erythrocyte Na+/Li+ CT was 4.5 (95% CI of 2.1-11.4). CONCLUSIONS: These results confirm those of previous studies and suggest that Na+/Li+ CT may be one of the predictors and risk factors for incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased Na+/Li+ CT activity may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop microalbuminuria and incipient diabetic nephropathy.
Effects of repeated hypoglycemia on cognitive function: a psychometrically validated reanalysis of the Diabetes Control and Complications Trial data.
Authors: Austin E J , Deary I J
Published: March 2007

OBJECTIVE: To test the conclusion that there is no association between multiple episodes of severe hypoglycemia and cognitive decrements by reanalyzing the data from the Diabetes Control and Complications Trial (DCCT) with psychometrically validated cognitive factors and to conduct a novel analysis of the association between individual differences in baseline cognitive ability and episodes of severe hypoglycemia documented after baseline. RESEARCH DESIGN AND METHODS: The factor structure of cognitive ability in the neuropsychological data from the DCCT study was derived. Four cognitive factors (spatial ability, processing speed, memory, and verbal ability) were extracted. Changes in patients' cognitive scores for each year of follow-up were obtained, and paired comparisons of these change scores were performed between groups experiencing zero and five or more hypoglycemic episodes. The association between cognitive ability at baseline and number of subsequent episodes of severe hypoglycemia was also examined. RESULTS: Repeated episodes of hypoglycemia were found not to be associated with cognitive decline in any of the validated cognitive factors. No significant association was found between prospectively documented numbers of severe hypoglycemic episodes and baseline cognitive ability level. CONCLUSIONS: Repeated episodes of hypoglycemia were not related to cognitive decrement, and initial mental ability level was not associated with eventual numbers of hypoglycemic episodes in this group of patients.
Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA).
Authors: Isomaa B , Almgren P , Henricsson M , Taskinen M R , Tuomi T , Groop L , Sarelin L
Published: March 2007

OBJECTIVE: To study the prevalence of chronic diabetic complications in patients with the slowly progressing autoimmune form of type 1 diabetes, also referred to as latent autoimmune diabetes in adults (LADA). RESEARCH DESIGN AND METHODS: We evaluated factors associated with chronic diabetic complications in 59 patients with GAD antibodies (GADAs) and age at onset of diabetes >35 years and in 59 GADA-negative type 2 diabetic patients. The prevalence of chronic complications was further compared with the prevalence in 111 type 1 diabetic patients. RESULTS: The LADA patients had lower BMI (P = 0.04), waist-to-hip ratio (P = 0.02 for men and P = 0.03 for women), and fasting C-peptide concentrations (P<0.001) higher HDL2 concentrations (P = 0.04), and less hypertension (58 vs. 75%, P = 0.05) than the type 2 diabetic patients. These differences were even more marked in patients with short disease duration. The prevalence of retinopathy (51 vs. 56%), neuropathy (29 vs. 27%), and microalbuminuria (27 vs. 29%) did not differ between the groups. The type 1 diabetic patients had lower prevalence of neuropathy (13%, P = 0.02) and higher prevalence of retinopathy (76%, P = 0.002) compared with the other groups. Neither the prevalence of coronary heart disease (CHD) (56 vs. 58%) nor cardiovascular mortality (7.4 vs. 12.4%, P = 0.2) significantly differed between the LADA and type 2 diabetic patients. In a multiple logistic regression analysis, glycemic control was associated with CHD (P = 0.02) in the LADA group but not in the type 2 diabetic group. CONCLUSIONS: Glycemic control is a stronger risk factor for cardiovascular disease in LADA patients than in patients with type 2 diabetes. This could be related to the lower prevalence of the metabolic syndrome seen in the former.
Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease.
Authors: Kilhovd B K , Berg T J , Birkeland K I , Thorsby P , Hanssen K F
Published: March 2007

OBJECTIVE: To investigate whether serum levels of advanced glycation end products (AGEs) and the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) are increased in patients with type 2 diabetes compared with nondiabetic control subjects and whether levels of AGEs and/or CML differ in patients with type 2 diabetes with or without coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Serum levels of AGEs and CML were measured with an immunoassay in 32 men and 21 women aged 59.3+/-6.2 years (means +/- SD) with type 2 diabetes for 7.3 + 3.1 years and in 17 men and 17 women aged 56.2+/-4.2 years without diabetes. Of the patients with diabetes, 18 had CHD. RESULTS: The serum levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects (median [5th-95th percentile]: AGEs 7.4 [4.4-10.9] vs. 4.2 [1.6-6.4] U/ml, P < 0.0001; CML 15.6 [5.6-29.9] vs. 8.6 [4.4-25.9] U/ml, P < 0.0001). The median level of AGEs but not CML was significantly increased in patients with type 2 diabetes and CHD compared with patients without CHD (8.1 [6.4-10.9] vs. 7.1 [3.5-9.8] U/ml, P = 0.03). There were significant positive correlations between serum levels of AGEs and CML in both patients and control subjects. CONCLUSIONS: Levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects, and levels of AGEs but not CML were significantly higher in patients with type 2 diabetes and CHD than in patients without diabetes. These results may indicate a role for non-CML AGEs in the development of macrovascular disease in patients with type 2 diabetes.
Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy.
Authors: Tarnow L , Rossing P , Nielsen F S , Fagerudd J A , Poirier O , Parving H H
Published: March 2007

OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect against coronary heart disease in nondiabetic and diabetic subjects. The aim of the present study was to evaluate these hypotheses in parents of a large group of type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated cardiovascular morbidity and mortality of parents of 163 type 1 diabetic patients with nephropathy and parents of 163 sex- and age-matched normoalbuminuric patients with type 1 diabetes. RESULTS: Kaplan-Meier curves showed that total parental mortality was significantly increased in parents of type 1 diabetic patients with nephropathy (121 of 244 [ approximately 50%] ) as compared with parents of normoalbuminuric type 1 diabetic patients (119 of 269 [approximately 44%]) (P = 0.008 [log-rank test]) partially due to an increase in cardiovascular deaths (48 of 244 [approximately 20%] vs. 42 of 269 [approximately 16%], P<0.05). In addition, more patients with nephropathy, as compared with the normoalbuminuric group, had at least one parent with fatal/nonfatal cardiovascular disease (46% [95% CI 38-54] vs. 36% [28-44], P = 0.05). Fathers of patients homozygous for the I-allele of the ACE/ID polymorphism had significantly less myocardial infarction as compared with other genotypes (P = 0.03), regardless of the nephropathic state of the offspring. CONCLUSIONS: Cardiovascular morbidity and early mortality clusters in parents of type 1 diabetic patients with diabetic nephropathy The ACE/ID polymorphism helps explain the increased morbidity from cardiovascular disease.
Impaired fasting glucose: how low should it go?
Authors: Shaw J E , Zimmet P Z , Hodge A M , de Courten M , Dowse G K , Chitson P , Tuomilehto J , Alberti K G
Published: March 2007

OBJECTIVE: Impaired fasting glucose (IFG) has been recently introduced as a stage of abnormal carbohydrate metabolism, but the evidence on which its glucose limits (fasting plasma glucose [FPG] 6.1-6.9 mmol/l) are based is not strong. The aim of this study was to determine if 6.1 mmol/l represents a clear cutoff in terms of the risk of future diabetes and in terms of elevated cardiovascular risk factor levels, and to examine the use of other lower limits of IFG. RESEARCH DESIGN AND METHODS: A population-based survey of the island of Mauritius was undertaken in 1987, with a follow-up survey 5 years later. On both occasions, an oral glucose tolerance test was performed and cardiovascular risk factors were measured. RESULTS: Data were available from 4,721 nondiabetic people at baseline, and from 3,542 at follow-up. At baseline, blood pressure, lipids, and obesity increased in a linear fashion with increasing FPG, with no evidence of a threshold effect. The risk of developing hypertension at follow-up was greater for those people with baseline FPG > or =6.1 mmol/l (P<0.001). The risk of developing diabetes at follow-up increased with increasing baseline FPG, but there was little evidence of a threshold near 6.1 mmol/l. CONCLUSIONS: Cardiovascular risk and risk of future diabetes increase continually with increasing FPG, and there is no threshold value on which to base a definition of IFG. If a lower limit of approximately 5.8 mmol/l is used, the category defines a group more similar to the group with impaired glucose tolerance, with regard to total prevalence and the risk of subsequent diabetes.
Dietary unsaturated fatty acids in type 2 diabetes: higher levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic acid-rich olive oil diet.
Authors: Madigan C , Ryan M , Owens D , Collins P , Tomkin G H
Published: March 2007

OBJECTIVE: The present study was undertaken to examine the effect of a polyunsaturated fat diet compared with an isocaloric Mediterranean-style monounsaturated fat diet. RESEARCH DESIGN AND METHODS: This was a randomized 2-week crossover study on either a high-polyunsaturated or a high-monounsaturated fat diet in 11 well-controlled diabetic men. Blood was taken fasting and for up to 8 h after a high fat meal. Lipoproteins were isolated by sequential ultracentrifugation. Apolipoprotein (apo) B48 and apo B100 were separated by PAGE. Fatty acids were analyzed by gas-liquid chromatography RESULTS: Fasting blood glucose and insulin levels were significantly higher on the linoleic acid diet compared with the oleic acid diet (P < 0.01 and P < 0.002, respectively). Plasma cholesterol and LDL cholesterol levels were also significantly higher on the linoleic acid diet (P < 0.001). Likewise, fasting chylomicron apo B48 and apo B100 (P < 0.05) and postprandial chylomicron and VLDL apo B48 and B100 (P < 0.05) were also higher on the linoleic acid diet. CONCLUSIONS: This study suggests that, in type 2 diabetes, an oleic acid-rich Mediterranean-type diet versus a linoleic acid-enriched diet may reduce the risk of atherosclerosis by decreasing the number of chylomicron remnant particles.
Linking pharmacy and laboratory data to assess the appropriateness of care in patients with diabetes.
Authors: Wetzler H P , Snyder J W
Published: March 2007

OBJECTIVE: To use pharmacy and laboratory data to assess diabetes care within a medical group and between medical groups and to determine dispensing patterns and the extent to which providers change therapy based on HbA1c results. RESEARCH DESIGN AND METHODS: Participating groups submitted 1 year of data for continuously enrolled patients. Required data included date of birth, all diabetes-specific prescriptions (oral hypoglycemic agents and insulin), date of prescription, National Drug Code, all HbA1c values, lower and upper normal limits, and date of testing. RESULTS: Few changes in therapy were noted despite the large percentages of patients with suboptimal control. Nearly 90% of the patients treated with medications received a monotherapy regimen involving one of three therapeutic agents: sulfonylureas, metformin, or insulin. More than three-fourths of the patients remained on the same therapy during the observation period despite the fact that 27% of these patients had HbA1c values > or = 8%. Nearly one-fifth (18%) of patients had an HbA1c level of > or = 8% and no further testing for at least 90 days after the "actionable" HbA1C result was obtained. Furthermore, 54% of patients with actionable HbA1c results did not have a change in therapy initiated after the result was available. CONCLUSIONS: The American Diabetes Association recommendations to act on HbA1c values > or = 8% and to follow up regularly on patients found to be in suboptimal control do not appear to be applied in a consistent manner based on the pharmacy and laboratory data analyzed in this sample.
A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes.
Authors: Raskin P , Klaff L , Bergenstal R , Hallé J P , Donley D , Mecca T
Published: March 2007

OBJECTIVE: To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS: Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS: Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.
Age-related macular degeneration in newly diagnosed type 2 diabetic patients and control subjects: a 10-year follow-up on evolution, risk factors, and prognostic significance.
Authors: Voutilainen-Kaunisto R M , Teräsvirta M E , Uusitupa M I , Niskanen L K
Published: March 2007

OBJECTIVE: To investigate the evolution of visual acuity, age-related macular degeneration (AMD), and its relation to 10-year cardiovascular mortality and risk factors in patients with newly diagnosed type 2 diabetes and control subjects. RESEARCH DESIGN AND METHODS: A 10-year prospective study consisting of a representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82 women) nondiabetic control subjects recruited from the population register was performed. The frequency of AMD was determined by grading of 45 degrees stereoscopic fundus photographs. The subjects were studied at baseline and after 5 and 10 years. RESULTS: By the 10-year follow-up, visual acuity had declined more markedly in the diabetic patients than in the control subjects. Although the frequency of AMD was nearly the same in both groups (11-19%), it decreased visual acuity earlier in the diabetic patients than in the control group. AMD at baseline predicted 10-year cardiovascular mortality independently of adjustment for other risk factors in the diabetic patients (odds ratio [95% CI] 4.7 [1.1-19.3], P = 0.033). CONCLUSIONS: Visual acuity deteriorated earlier in newly diagnosed type 2 diabetic patients than in the control group although the cross-sectional frequency of AMD was nearly the same in both groups. Interestingly, AMD was an independent risk factor for cardiovascular mortality in type 2 diabetic patients, but the background mechanism(s) behind this association is unknown.
Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition.
Authors: Brown M D , Korytkowski M T , Zmuda J M , McCole S D , Moore G E , Hagberg J M
Published: March 2007

OBJECTIVE: The effects of combined physical activity and hormone replacement therapy (HRT) on insulin sensitivity in postmenopausal (PM) women are unclear. The purpose of the study was to test the following hypotheses: 1) PM women who have undergone vigorous exercise training have greater insulin sensitivity than PM women who are physically active and PM women who are sedentary, and 2) PM women using HRT have greater insulin sensitivity than PM women not using HRT. We also sought to determine whether body composition or cardiovascular fitness was the stronger predictor of insulin sensitivity in these women. RESEARCH DESIGN AND METHODS: Three groups of PM women classified as sedentary (n = 18), physically active (n = 19), and athletic (n = 23) underwent an insulin-modified frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) and dual-energy X-ray absorptiometry to determine body composition. RESULTS: There was a significant association between both physical activity (P = 0.036) and HRT (P = 0.007) and fasting plasma insulin levels. The athletic PM women had the lowest plasma insulin levels and the highest SI. Across all physical activity levels, PM women using HRT (n = 29) had significantly lower fasting plasma insulin levels and a lower SI than PM women not using HRT (n = 31). HRT was significantly (P = 0.025) associated with intravenous glucose tolerance (KG); the women not using HRT had a higher K(G); than the PM women using HRT (0.83 +/- 0.08 vs. 0.60 +/- 0.05% per minute). Percent body fat (r = -0.37, P = 0.004) and VO2max (r = 0.35, P = 0.007) were similar predictors of SI. CONCLUSIONS: We conclude that, although overall HRT was associated with an attenuated SI, vigorous exercise training was independently associated with the greatest SI. In addition, PM women using HRT may benefit from having lower plasma insulin levels, but they may also have a lower SI.
Serum markers of oxidative stress and severity of diabetic retinopathy.
Authors: Hartnett M E , Stratton R D , Browne R W , Rosner B A , Lanham R J , Armstrong D
Published: March 2007

OBJECTIVE: To compare serum markers of oxidative stress with diabetic retinopathy severity RESEARCH DESIGN AND METHODS: This cross-sectional study compared patients with types 1 and 2 diabetes with control subjects in western New York and Pennsylvania. Retinopathy severity was graded from funduscopic fields based on the Early Treatment of Diabetic Retinopathy Study. Serum samples were analyzed for thiobarbituric acid-reacting substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, creatinine, HbA1, and triglycerides. Appropriate analysis of covariance models were performed. RESULTS: TBARS (P = 0.019), triglyceride (P = 0.004), and glucose and HbA1 (both P<0.001) levels were elevated in diabetic patients compared with those in control subjects. SOD (P = 0.003) and GSH-Px (P = 0.046) levels were lower in diabetic patients than in control subjects. No correlation existed between SOD levels and either glucose or HbA1 levels. No significant associations existed between levels of TBARS, SOD, or GSH-Px and severity of diabetic retinopathy There was a significant association between poorer visual acuity and worse retinopathy (P = 0.009), which was only partly explained by macular edema. CONCLUSIONS: Increased levels of TBARS and decreased levels of SOD and GSH-Px were found in diabetic patients compared with those in control subjects, but no significant associations were found between the levels of these substances and severity of retinopathy When duration and type of diabetes and serum HbA1 levels were taken into account, only visual acuity remained associated with more severe retinopathy.
Is "sugar" the same as diabetes? A community-based study among rural African-Americans.
Authors: Schorling J B , Saunders J T
Published: March 2007

OBJECTIVE: To determine if differing beliefs about high blood glucose exist and are associated with blood glucose control among rural African-Americans. RESEARCH DESIGN AND METHODS: A community-based sample of rural African-Americans completed a survey, and a subsample underwent a subsequent screening that included glucose and GHb measurement. Participants were asked if they thought they had diabetes or sugar-diabetes on the survey; "sugar" was added to the screening along with specific questions about this condition. RESULTS: A total of 1,031 people completed the survey, and 403 the screening exam. The total prevalence of diabetes was 13.6% for men and 15.5% for women. Among those who reported having one of the three conditions, 64% said they had diabetes, 7% sugar-diabetes, and 29% sugar. There was a discrepancy between the survey and screening in that 31% of subjects who answered "yes" to whether they had sugar at the screening had answered "no" to the survey question about diabetes. Subjects who believed they had sugar felt their condition was less serious and had higher glucose levels than those who said they had diabetes. CONCLUSIONS: Diabetes was very common in this population. Over one-fourth of those with diabetes believed they had the condition "sugar." Efforts are needed to improve control of diabetes in this population and should consider these disparate health beliefs.
Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes.
Authors: Watson J M , Jenkins E J , Hamilton P , Lunt M J , Kerr D
Published: March 2007

OBJECTIVE: To examine the influence of caffeine on the frequency and perception of hypoglycemia in "free-living" patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 34 patients with type 1 diabetes were recruited for a prospective randomized placebo-controlled double-blind study. After a lead-in phase and while adhering to a low-caffeine diet, subjects were randomized to capsules containing either 200 mg caffeine or matched placebo with crossover at 3 months. Hypoglycemic episodes were monitored throughout with capillary blood glucose readings and a symptom questionnaire. During the study, measurements of blood pressure, middle cerebral artery blood velocity (a surrogate measure of cerebral blood flow), cognitive function (via a four-choice reaction time test), HbAlc levels, and lipid profiles were taken at the beginning and end of each phase. RESULTS: Throughout the study, no changes were evident regarding glycemic control or lipid profile. The number of symptomatic episodes was greater with caffeine (1.3 vs. 0.9 episodes/week; P < 0.03) and was associated with more intense warning symptoms (29 vs. 26 total symptom score; P < 0.05). For women, caffeine ingestion caused a modest pressor response (115 vs. 110 mmHg; P < 0.01). Four-choice reaction time improved slightly with caffeine supplementation (P < 0.05). CONCLUSIONS: Ingestion of modest amounts of caffeine enhances the intensity of hypoglycemia warning symptoms in patients with type 1 diabetes without altering the prevailing standard of glycemic control or increasing the incidence of severe hypoglycemic episodes.
Heart rate in relation to insulin sensitivity and insulin secretion in nondiabetic subjects.
Authors: Festa A , D'Agostino R , Hales C N , Mykkänen L , Haffner S M
Published: March 2007

OBJECTIVE: Elevated heart rate has been predictive of cardiovascular disease and has been proposed as a global index of the autonomic nervous system influence on the heart. Hyperinsulinism has been shown to trigger sympathetic activity experimentally; however, the clinical and epidemiological data on the association of heart rate with hyperinsulinism and insulin resistance are conflicting. RESEARCH DESIGN AND METHODS: Insulin sensitivity (S(I)) and the acute insulin response (AIR) to glucose were assessed by a frequently sampled intravenous glucose tolerance test and related to resting heart rate in the tri-ethnic nondiabetic population (n = 1,000) of the Insulin Resistance Atherosclerosis Study. RESULTS: Heart rate was related to fasting insulin (r = 0.20), intact proinsulin (r = 0.15), split proinsulin (r = 0.17), and AIR (r = 0.18), and an inverse relation was found between heart rate and S(I) (r = -0.19) (all P values <0.0001, adjusted for age, sex, ethnicity, glucose tolerance status, and smoking). In a multiple linear regression analysis (adjusting for age, sex, ethnicity, clinical center, glucose tolerance status, and smoking), heart rate was significantly and independently associated with AIR, proinsulin, and S(I). CONCLUSIONS: Proinsulin, acute insulin secretion, and S(I) are associated with heart rate in nondiabetic subjects.
Health care and health status and outcomes for patients with type 2 diabetes.
Authors: Harris M I
Published: March 2007

OBJECTIVE: To evaluate access and utilization of medical care, and health status and outcomes that would be influenced by recent medical care, in a representative sample of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A national sample of 733 adults with type 2 diabetes was studied from 1991 to 1994 in the Third National Health and Nutrition Examination Survey. Structured questionnaires and clinical and laboratory assessments were used to determine the frequencies of physician visits, health insurance coverage, screening for diabetes complications, treatment for hyperglycemia, hypertension, and dyslipidemia; and the proportion of patients who met treatment goals and established criteria for health outcome measures including hyperglycemia, albuminuria, obesity, hypertension, and dyslipidemia. RESULTS: Almost all patients had 1 source of primary care (95%), 2 or more physician visits during the past year (88%), and health insurance coverage (91%). Most (76%) were treated with insulin or oral agents for their diabetes, and 45% of those patients taking insulin monitored their blood glucose at least once per day The patients were frequently screened for retinopathy (52%), hypertension (88%), and dyslipidemia (84%). Of those patients with hypertension, 83% were diagnosed and treated with antihypertensive agents and only 17% were undiagnosed or untreated; most of the patients known to have dyslipidemia were treated with medication or diet (89%). Health status and outcomes were less than optimal: 58% had HbA1c >7.0, 45% had BMI >30, 28% had microalbuminuria, and 8% had clinical proteinuria. Of those patients known to have hypertension and dyslipidemia, 60% were not controlled to accepted levels. In addition, 22% of patients smoked cigarettes, 26% had to be hospitalized during the previous year, and 42% assessed their health status as fair or poor. CONCLUSIONS: Rates of health care access and utilization, screening for diabetes complications, and treatment of hyperglycemia, hypertension, and dyslipidemia in type 2 diabetes are high; however, health status and outcomes are unsatisfactory. There are likely to be multiple reasons for this discordance, including intractability of diabetes to current therapies, patient self-care practices, physician medical care practices, and characteristics of U.S. health care systems.
Capture-recapture method in the epidemiology of type 2 diabetes: a contribution from the Verona Diabetes Study.
Authors: Verlato G , Muggeo M
Published: March 2007

OBJECTIVE: The present investigation used data from the Verona Diabetes Study to verify a main assumption of the capture-recapture method (source independence) and to characterize the subgroup of known diabetic patients missed by all sources whose number is estimated by the capture-recapture method. RESEARCH DESIGN AND METHODS: The Verona Diabetes Study identified 7,148 type 2 diabetic patients on 31 December 1986 using 3 different sources: family physicians, a diabetes center, and a drug prescription database. Completeness of ascertainment was estimated with traditional methods based on the hypergeometric distribution and with a log-linear model. RESULTS: Identification sources were not independent because the drug prescription database was positively related to family physicians and negatively related to the diabetes center (P < 0.001). Thus, completeness of ascertainment was overestimated (87.5% [95% CI 86.3-88.8]) when using only family physicians and the drug prescription database and underestimated (45.9% [43.9-48.1]) when using only the diabetes center and the drug prescription database. Because of characteristics contributing to variable "catchability" (probability of ascertainment), the estimated proportion of ascertainment increased with increasing time since diagnosis from 65.6% in the first tertile (<6 years) to 91.5% in the third tertile (>12 years); moreover, the ascertainment was estimated to be nearly complete (97.9%) for insulin-treated patients and scanty (28.9%) for diet-treated patients. CONCLUSIONS: Because identification sources are likely to be dependent, the capture-recapture method should be used with caution in diabetes epidemiology and possibly when at least 3 sources are available. The subgroup of diabetic patients whose existence is inferred by this technique likely consists of newly diagnosed patients with mild disease severity.
Effect of pinitol treatment on insulin action in subjects with insulin resistance.
Authors: Davis A , Christiansen M , Horowitz J F , Klein S , Hellerstein M K , Ostlund R E
Published: March 2007

OBJECTIVE: Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl-D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m2) with diet-treated type 2 diabetes or glucose intolerance (HbA1c = 6.8%). RESEARCH DESIGN AND METHODS: There were 22 subjects randomized to receive either pinitol 20 mg x kg(-1) x day(-1) (n = 12) or placebo (n = 10) in a 28-day double-blinded trial. RESULTS: No toxicity due to the pinitol was observed during the study The sensitivity of glucose and lipid metabolism to insulin were assessed by measurement of whole-body glucose, palmitate, and glycerol kinetics during basal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were made at baseline and again at the end of the study Final plasma levels of pinitol were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 micromol/l, P < 0.0001) and D-chiro-inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.02 micromol/l, P < 0.0001) greater in the pinitol group compared with placebo. CONCLUSIONS: Four weeks of pinitol treatment did not alter baseline glucose production, insulin-mediated glucose disposal, or rates of appearance of free fatty acids and glycerol in plasma. We conclude that plasma levels of both pinitol and D-chiro-inositol are very responsive to pinitol ingestion, but insulin sensitivity does not increase after pinitol treatment in individuals with obesity and mild type 2 diabetes.
Development and validation of a questionnaire to evaluate patient satisfaction with diabetes disease management.
Authors: Paddock L E , Veloski J , Chatterton M L , Gevirtz F O , Nash D B
Published: March 2007

OBJECTIVE: To develop a reliable and valid questionnaire to measure patient satisfaction with diabetes disease management programs. RESEARCH DESIGN AND METHODS: Questions related to structure, process, and outcomes were categorized into 14 domains defining the essential elements of diabetes disease management. Health professionals confirmed the content validity. Face validity was established by a patient focus group. The questionnaire was mailed to 711 patients with diabetes who participated in a disease management program. To reduce the number of questionnaire items, a principal components analysis was performed using a varimax rotation. The Scree test was used to select significant components. To further assess reliability and validity; Cronbach's alpha and product-moment correlations were calculated for components having > or =3 items with loadings >0.50. RESULTS: The validated 73-item mailed satisfaction survey had a 34.1% response rate. Principal components analysis yielded 13 components with eigenvalues > 1.0. The Scree test proposed a 6-component solution (39 items), which explained 59% of the total variation. Internal consistency reliabilities computed for the first 6 components (alpha = 0.79-0.95) were acceptable. CONCLUSIONS: The final questionnaire, the Diabetes Management Evaluation Tool (DMET), was designed to assess patient satisfaction with diabetes disease management programs. Although more extensive testing of the questionnaire is appropriate, preliminary reliability and validity of the DMET has been demonstrated.
Adaptation of cognitive function to hypoglycemia in healthy men.
Authors: Fruehwald-Schultes B , Born J , Kern W , Peters A , Fehm H L
Published: March 2007

OBJECTIVE: Antecedent hypoglycemia reduces hypoglycemic counterregulation and symptoms, thereby provoking the hypoglycemia unawareness syndrome. The effects of antecedent hypoglycemia on hypoglycemia-induced cognitive dysfunction are less well established. RESEARCH DESIGN AND METHODS: To determine whether antecedent hypoglycemia also reduces hypoglycemic cognitive dysfunction, we performed stepwise hypoglycemic clamp experiments (4.1, 3.6, 3.1, and 2.6 mmol/l) during a 6-h period in 30 young healthy men. A total of 15 subjects additionally received a 2.5-h antecedent hypoglycemic clamp (3.1 mmol/l) on the preceding day (prior-hypo group), whereas the other 15 subjects did not (control group). Cognitive function was assessed by auditory-evoked brain potentials (AEBPs) and reaction time during a vigilance task and short-term memory recall. Tests were performed during the stepwise hypoglycemic clamp at baseline and at each hypoglycemic plateau. RESULTS: In both groups, performance on all measures of cognitive function deteriorated during stepwise hypoglycemia (all P < 0.01). However, after antecedent hypoglycemia, the hypoglycemia-induced decrease in the amplitude of the P3 of the AEBP was distinctly reduced compared with the control condition (P < 0.05). Also, short-term memory performance was less impaired in the prior-hypo group than in the control group (P < 0.005), and a minor hypoglycemic impairment of reaction time (P < 0.05) was evident in the prior-hypo group. CONCLUSIONS: Data provide evidence that a single episode of mild antecedent hypoglycemia (3.1 mmol/l) attenuates several aspects of cognitive dysfunction during subsequent hypoglycemia 18-24 h later.
Relationship between diabetes and mortality: a population study using record linkage.
Authors: Morgan C L , Currie C J , Peters J R
Published: March 2007

OBJECTIVE: To determine patterns and causes of mortality for patients with diabetes in a district health authority RESEARCH DESIGN AND METHODS: The study used cross-sectional record linkage, combining an electronic death register with a diabetic patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all diabetic deaths between 1993 and 1996. RESULTS: Of 1,694 deaths in patients with known diabetes, only 674 (39.8%) had diabetes recorded as an immediate or antecedent cause of death. Mortality rates were 41.8 per 1,000 for the diabetic population and 10.1 per 1,000 for the nondiabetic population. The standard mean ratio for the diabetic population was 1.24 (95% CI 1.12-1.35), with the risk of mortality relative to the nondiabetic population decreasing with age. Males with diabetes lost an average of 7.0 years from the year of diagnosis, and females with diabetes lost an average of 7.5 years. The most common cause of death was cardiovascular disease, which accounted for 49.1% of deaths in the diabetic population. CONCLUSIONS: Diabetes is recorded as a cause of death on a minority of death certificates for patients with diabetes. Using death certificates in isolation, therefore, is a poor method of estimating diabetic mortality, but results can be improved with the use of record linkage techniques. Patients with diabetes have an excess risk of mortality compared with the nondiabetic population. Life-years lost for patients with diabetes is strongly related to age at diagnosis and is a means of expressing mortality without relying on accurate prevalence data.