bluuebunny/crossref_metadata_2025 huggingface dataset:
Stratifying Patients at Risk of Diabetic Complications: An integrated look at clinical, socioeconomic, and care-related factors
Authors: Nicolucci Antonio , Carinci Fabrizio , Ciampi Antonio ,   On behalf of the SID-AMD Italian Study Group for the Implementation of the St. Vincent Declaration
Published: March 2007

OBJECTIVE

The aim of this study was to identify subgroups of patients for whom the interactions among clinical, socioeconomic, and care-related factors determine a substantial increase in the risk of developing long-term diabetic complications.

RESEARCH DESIGN AND METHODS

We performed a case-control study aimed at identifying and quantifying the risk factors for the development of major diabetic complications (eye, renal, and lower limb complications) in type 1 and type 2 diabetic patients. A total of 886 patients with renal, eye, or lower limb complications and 1,888 control subjects were enrolled in 35 diabetes outpatient clinics and 49 general practitioners' offices in 17 out of the 20 Italian regions. The main results were obtained using recursive partitioning and amalgamation (RECPAM), a technique that attempts to integrate the advantages of main effect logistic regression and tree-growing.

RESULTS

The application of RECPAM led to the detection of important interactions involving clinical, socioeconomic, and care-related characteristics and allowed the identification of internally homogeneous subgroups characterized by a marked difference in the risk of developing major complications. In type 1 diabetic patients, the interaction between hypertension and smoking habits led to a dramatic increase in the complication risk, while in type 2 diabetic subjects, a poor compliance with visit scheduling was the most important predictor of complications. Furthermore, a marked difference in the risk profile was associated with patient characteristics (age, years of education, occupation).

CONCLUSIONS

In the definition of the risk profile for each individual patient, socioeconomic status and level of education need to be taken under serious consideration, since they can determine a complication risk not dissimilar from hard clinical variables, such as hypertension and diabetes duration. Specific educational interventions, targeted to the socially disadvantaged strata of the population, need to be designed and implemented.
Metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes.
Authors: Meneilly G S , Elliott T
Published: March 2007

OBJECTIVE: We conducted this study to assess the metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Healthy control subjects (9 middle-aged, aged 42 +/- 2 years, BMI 33 +/- 1 kg/m2; 10 elderly, aged 71 +/- 1 years, BMI 29 +/- 1 kg/m2) and patients with type 2 diabetes (11 middle-aged, aged 43 +/- 2 years, BMI 34 +/- 2 kg/m2; 23 elderly, aged 73 +/- 1 years; BMI 30 +/- 1 kg/m2) underwent a 3-h oral glucose tolerance test (OGTT), a 2-h hyperglycemic glucose clamp, and a 3-h euglycemic glucose clamp study with tritiated glucose methodology to measure hepatic glucose production and peripheral disposal rates. RESULTS: Middle-aged and elderly control subjects and patients with diabetes were similar in percentage of body fat. Waist-to-hip ratio was greater in elderly patients with diabetes than in elderly control subjects (P < 0.01), but was similar in both middle-aged groups. VO2max was less in control subjects than in both middle-aged and elderly patients with diabetes (P < 0.05). Insulin responses during the OGTT were similar in elderly control subjects and patients with diabetes, but were less in middle-aged patients with diabetes than in control subjects (305 +/- 49 vs. 690 +/- 136 pmol/l, P < 0.01). Patients with type 2 diabetes had absent first-phase insulin responses during the hyperglycemic clamp. Second-phase (80-120 min) insulin values were similar in elderly patients and control subjects, but were reduced in middle-aged patients with diabetes compared with control subjects (285 +/- 35 vs. 894 +/- 143 pmol/l, P < 0.0001). During the euglycemic clamp, basal and steady-state (150-180 min) hepatic glucose output values were less in middle-aged control subjects than in patients with diabetes (basal, 3.03 +/- 0.10 vs. 3.69 +/- 0.09 mg.kg-1 lean body mass.min-1, P < 0.0001; steady-state, 0.72 +/- 0.10 vs. 1.84 +/- 0.20 mg.kg-1 lean body mass.min-1, P < 0.0001). Basal and steady-state hepatic glucose output values were similar in elderly patients and control subjects. Finally, steady-state (150-180 min) glucose disposal rates were higher in control subjects than in patients with diabetes in both the middle-aged (7.51 +/- 0.85 vs. 4.62 +/- 0.24 mg.kg-1 lean body mass.min-1, P < 0.01) and elderly (9.91 +/- 0.61 vs. 6.78 +/- 0.60 mg.kg-1 lean body mass.min-1, P < 0.01) groups. CONCLUSIONS: We conclude that type 2 diabetes in obese middle-aged subjects is characterized by impaired glucose-induced insulin release, altered regulation of hepatic glucose output, and resistance to insulin-mediated glucose disposal. In contrast, the primary defect in elderly obese patients with type 2 diabetes is resistance to insulin-mediated glucose disposal. Our findings may have important therapeutic implications for these patient populations.
Optimal administration of lispro insulin in hyperglycemic type 1 diabetes.
Authors: Rassam A G , Zeise T M , Burge M R , Schade D S
Published: March 2007

OBJECTIVE: Lispro is a new rapidly absorbed insulin analog. At present, there are no recommendations for the optimal injection time of lispro insulin in hyperglycemic patients. In contrast to normoglycemic patients with diabetes, we hypothesized that injection of lispro insulin 15-30 min before meal ingestion would improve postprandial glucose excursion in hyperglycemic diabetic subjects. RESEARCH DESIGN AND METHODS: In 48 randomized overnight studies, 12 healthy adult type 1 diabetic patients received lispro insulin 0.15 U/kg admixed with human ultralente 0.2 U/kg (as background insulin) subcutaneously at minutes (-30, -15, 0, and +15) relative to the ingestion of an American Diabetes Association breakfast of 8.6 kcal/kg. Pre-breakfast hyperglycemia of 10.2 +/- 0.2 mmol/l was established before the study by continuous overnight infusion of intravenous insulin, which was stopped 30 min before lispro insulin injection. Glucose and insulin levels were measured every 30 min for 5 h after breakfast. RESULTS: Results demonstrated that postprandial glucose excursion was reduced when lispro insulin was administered 15 or 30 min before the meal compared with lispro insulin injected at the meal (P < 0.002). The postprandial glucose excursion (millimoles per liter per hour) was -6.4 +/- 3 for the -30-min group, -5.1 +/- 2.9 for the -15-min group, 3.4 +/- 4.1 for the 0-min group, and 5.7 +/- 4.4 for the +15-min group. Although injecting lispro insulin at 30 min before the meal resulted in a significant reduction in postprandial glycemia, it was accompanied by loss of glucose control at 4 h postmeal in two subjects. CONCLUSIONS: Optimization of lispro insulin in hyperglycemic patients requires timing of the insulin injection at least 15 min before the meal.
Predicting expenditures for Medicare beneficiaries with diabetes. A prospective cohort study from 1994 to 1996.
Authors: Krop J S , Saudek C D , Weller W E , Powe N R , Shaffer T , Anderson G F
Published: March 2007

OBJECTIVE: To describe health care expenditures and utilization patterns among older adults with diabetes and to examine factors associated with expenditures over a 3-year period. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of health care expenditures and utilization by diabetic patients from a random nationwide sample of aged Medicare beneficiaries from 1994 to 1996. All services covered by the Medicare program were examined. Multivariate regression was used to assess the contribution of patient characteristics in 1994 on Part B, inpatient, and total expenditures in 1995 and 1996. RESULTS: Per capita expenditures for beneficiaries with diabetes (n = 169,613) were 1.7 times greater than those for those beneficiaries without diabetes (n = 968,832) in 1994. This ratio remained fairly constant over the 2 years of follow-up. Expenditures for beneficiaries with diabetes were highly skewed. However, few of these individuals remained in the highest expenditure quintile over the 2 years of follow-up. Using multiple regression analysis to adjust for demographic and clinical characteristics, we were able to explain 7% of the variation in total expenditures in 1995 and 6% of the variation in 1996. Using the same model, we were able to explain 10.7% of the variation in Part B expenditures in 1995 and 8% in 1996. CONCLUSIONS: Beneficiaries with diabetes are consistently more expensive than beneficiaries without diabetes. Demographic and clinical factors at baseline are able to predict only a small portion of future expenditures among this population, and the most expensive patients in one year were often not the most expensive in subsequent years. More work is necessary to assure equitable risk adjustment in the calculation of capitation rates for health plans and practitioners who specialize in the care of individuals with diabetes.
Progression to diabetes in relatives with islet autoantibodies. Is it inevitable?
Authors: Gardner S G , Gale E A , Williams A J , Gillespie K M , Lawrence K E , Bottazzo G F , Bingley P J
Published: March 2007

OBJECTIVE: A large cohort of family members with islet cell antibodies (ICA) > or = 20 Juvenile Diabetes Foundation units (JDF U) was examined to determine whether there was a subgroup at low risk of progression to diabetes; whether risk of progression changed over time; and whether rate of progression to diabetes varied according to age, islet autoantibodies, and genetic markers of susceptibility. RESEARCH DESIGN AND METHODS: Individuals with ICA > or = 20 JDF U were identified from 4,423 family members recruited to prospective family studies in the U.K. Subjects were followed for up to 18 years. Antibodies to insulin, GAD, and IA-2 were measured in the first sample, and HLA class II typing was performed. RESULTS: Of 147 family members with ICA > or = 20 JDF U on at least one occasion, 29 developed type 1 diabetes after a median of 3.2 years (maximum 18.1). The cumulative risk of developing diabetes within 15 years was 47% (95% CI 28-67) for all family members with ICA > or = 20 JDF U, 2.8% (0-8.2) for those with ICA alone, and 66% (44-87) for those with at least one additional autoantibody marker. There were no differences in age, HLA class II type, or levels of ICA, insulin autoantibodies, or IA-2 antibodies between those who developed diabetes within 5 years of testing and those who developed diabetes after this time. GAD antibody levels we ..., however, higher in those who progressed more slowly. CONCLUSIONS: Family members with ICA alone are at low risk of progression to diabetes. Rapid development of disease after ICA detection could not be distinguished from delayed development on the basis of autoantibodies or markers of genetic susceptibility, and those with multiple antibodies remained at high risk throughout long-term follow-up. This suggests that all family members with multiple islet autoantibodies are destined to develop autoimmune diabetes.
Frequency of liver disease in type 2 diabetic patients treated with oral antidiabetic agents.
Authors: Jick S S , Stender M , Myers M W
Published: March 2007

OBJECTIVE: We evaluated liver disease in conventionally treated type 2 diabetic patients to provide a reference against which reports of liver disease related to novel oral antidiabetic treatments could be compared. RESEARCH DESIGN AND METHODS: In this follow-up study, patients with type 2 diabetes who were treated with oral antidiabetic agents were identified from the U.K.-based General Practice Research Database and were followed to determine whether they developed liver disease. The specific types and etiologies of liver disorders were determined. Incidence rates were calculated based on the accumulated exposure time to oral antidiabetic agents. RESULTS: Among 44,406 type 2 diabetic patients, 605 had a computer diagnosis of liver disease with an incidence rate of 53.2/10,000 person-years (95% CI 49.2-57.6). Of the 605 subjects, 186 had nonsymptomatic, mild, and transient liver disorders; 249 had a predisposing condition; and 113 had another cause for the disease. A total of 57 cases were possibly drug induced with an incidence rate of 5.0/10,000 person-years (3.9-6.5). Of the cases, 11 were attributed to other drugs, 8 were attributed to fatty liver disease of diabetes, and the remaining cases were attributed to uncertain causes. Oral antidiabetic agents were continued in 51 of these 57 cases, and we could not rule out oral antidiabetic agents as a cause of liver disease in 2 cases with an incidence rate of 0.2/10,000 person-years (< 0.1-0.6). CONCLUSIONS: In this population, the background incidence of liver disease was high. Most cases involved other systemic diseases that may cause liver disease.
Phenotypic characteristics of early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young (MODY) genes.
Authors: Doria A , Yang Y , Malecki M , Scotti S , Dreyfus J , O'Keeffe C , Orban T , Warram J H , Krolewski A S
Published: March 2007

OBJECTIVE: To investigate whether there are forms of early-onset autosomal-dominant type 2 diabetes that are distinct from typical maturity-onset diabetes of the young (MODY) and to characterize their phenotypic characteristics. RESEARCH DESIGN AND METHODS: The study included 220 affected subjects from 29 families in which early-onset type 2 diabetes occurred in multiple generations and was not linked to known MODY genes (MODY gene-negative families). All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications. For comparison, 79 affected carriers of MODY3 (hepatocyte nuclear factor [HNF]-1 alpha) mutations were similarly examined. RESULTS: Subjects from MODY gene-negative pedigrees were diagnosed with diabetes at an older age (36 +/- 17 vs. 21 +/- 10 years, P = 0.0001) and were more frequently obese (52 vs. 18%, P = 0.0001) than MODY3 individuals. MODY gene-negative patients who were insulin treated required more exogenous insulin than did MODY3 subjects (0.7 +/- 0.4 vs. 0.45 +/- 0.2 U.kg-1.day-1, P = 0.04), despite similar C-peptide levels. Among subjects not treated with insulin, MODY gene-negative subjects had significantly higher serum insulin levels, both fasting (16.5 +/- 15 vs. 6.5 +/- 5 microU/ml, P = 0.027) and 2 h after a glucose load (53 +/- 44 vs. 11 +/- 10, P = 0.002). They also had higher serum triglycerides (P = 0.02), higher cholesterol levels (P = 0.02), more hypertension (P = 0.0001), and more nephropathy (P = 0.001). Differences persisted when families were matched for age at diagnosis. CONCLUSIONS: Our findings indicate the existence of forms of early-onset autosomal-dominant type 2 diabetes that are distinct from MODY and are frequently characterized by insulin resistance, similar to later-onset type 2 diabetes. Because of the Mendelian pattern of inheritance, the goal of identifying the genes involved in these forms of diabetes appears to be particularly feasible.
Glycemic control in patients with diabetes in Finland.
Authors: Valle T , Koivisto V A , Reunanen A , Kangas T , Rissanen A
Published: March 2007

OBJECTIVE: To evaluate the quality of diabetes care at a national level in Finland, using level of glycemia as a determinant of success in treatment. RESEARCH DESIGN AND METHODS: Physicians and diabetes nurses in 76 randomly selected clinics (59 primary care units and 17 hospitals) evenly covering the whole of Finland were asked to fill in a questionnaire asking for data based on the 1993 medical records of a random sample of 50 diabetic patients from each center (total n = 3,800). HbAlc was used as an index of glycemic control. RESULTS: Information on 3,195 (84%) diabetic patients was received. HbAlc was measured in 67% of the patients in 1993. The mean HbAlc in the whole population was 8.6 +/- 1.9% (normal range 4-6%). Some 25% of patients had HbAlc < or = 7.3%, while 25% had HbAlc > or = 9.7%. The mean HbAlc was 8.8 +/- 1.9% in type 1 and 8.5 +/- 1.9% in type 2 diabetic patients. There was no sex difference in the HbAlc level in type 1 diabetic patients. However, male type 2 diabetic patients had better glycemic control than female patients (8.3 +/- 1.9 vs. 8.8 +/- 1.9%, P < 0.0001). The sex difference was independent of the type of therapy. The mean level of glycemic control was lowest among individuals with the shortest duration of diabetes. After 7-9 years after the diagnosis, there was no change in the mean level of glycemia. CONCLUSIONS: Average glycemic control is poor in a majority of the diabetic patients in Finland. Better treatment strategies and methods should be used to improve glycemic control and to reduce long-term complications.
Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.
Authors: Thrailkill K M , Quattrin T , Baker L , Kuntze J E , Compton P G , Martha P M
Published: March 2007

OBJECTIVE: To study the effects of 12 weeks of cotherapy with recombinant human IGF-I (rhIGF-I) and insulin on glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: The study population consisted of 223 patients who ranged in age from 11-66 years and were randomized in a double-blind study to receive 12 weeks of treatment with twice-daily subcutaneous injections of placebo (n = 54), or rhIGF-I at a dose (A.M/P.M) of 40/40 micrograms/kg (n = 56), 80/40 micrograms/kg (n = 57), or 80/60 micrograms/kg (n = 56), while continuing to receive standard insulin therapy. Patients were instructed to test blood glucose levels four times daily and adjust insulin doses to optimize blood glucose control. HbAlc, insulin requirements, body weight, and parameters of the IGF-IGF-binding protein axis were assessed before and during treatment. RESULTS: All groups were comparable at baseline with respect to mean age, gender distribution, duration of diabetes, HbAlc, and BMI. Cotherapy with rhIGF-I/insulin produced a mean decrease in HbAlc of 1.2%, compared with a 0.7% decrease in HbAlc for patients receiving intensified insulin therapy alone (P < or = 0.01). Subjects receiving rhIGF-I/insulin cotherapy also decreased their daily insulin usage by 11-19%, compared with a 7% increase in insulin usage reported by the placebo group. Moreover, the incidence of hypoglycemia was similar in subjects treated with rhIGF-I/Insulin cotherapy compared with those treated with insulin alone, despite the better glycemic control of the former group. The 40/40 dose of rhIGF-I was well tolerated. Higher doses of rhIGF-I did not further improve efficacy yet were associated with unacceptable levels of adverse events, including edema, jaw pain, and early worsening of retinopathy. CONCLUSIONS: These results demonstrate that rhIGF/insulin cotherapy improves glycemic control in patients with type 1 diabetes better than optimized insulin management alone; longer-term trials would be required to determine an acceptable benefit-risk profile.
Implications of new diagnostic criteria for abnormal glucose homeostasis in women with previous gestational diabetes.
Authors: Kousta E , Lawrence N J , Penny A , Millauer B A , Robinson S , Dornhorst A , de Swiet M , Steer P J , Grenfell A , Mather H M , Johnston D G , McCarthy M I
Published: March 2007

OBJECTIVE: To determine the consequences of applying revised American Diabetes Association (ADA) (1997) and World Health Organization (WHO) (1998) recommendations for the classification of glucose intolerance in women with previous gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: There were 192 women with previous GDM who took an oral glucose tolerance test (OGTT) 1-86 months after delivery and were classified by WHO (1985), ADA (1997, fasting glucose), and revised WHO (1998) guidelines. RESULTS: Among the 165 women without a preexisting diagnosis of diabetes, WHO-1985 and ADA-1997 provided similar estimates of diabetes prevalence (13.3% vs. 11.5%) but widely differing estimates of impaired glucose homeostasis (31.5% impaired glucose tolerance [IGT] by WHO-1985 vs. 10.9% impaired fasting glucose by ADA-1997 criteria). Overall, 56 women (34%) showed a classification discrepancy between WHO-1985 and ADA-1997 criteria, including 44 with normal fasting glucose by ADA-1997 criteria, but abnormal 2-h glucose by WHO-1985 criteria (40 IGT, 4 diabetes). The cardiovascular risk profile of these women was more favorable than that of 18 women with impaired fasting glucose. WHO-1998 recommendations reproduced ADA-1997 findings when used as a fasting screen, but behaved similarly to WHO-1985 criteria when 2-h glucose values were also analyzed. CONCLUSIONS: All criteria produced similar estimates of diabetes prevalence. However, analyses based on a single fasting glucose screen (and a threshold of 6.1 mmol/l) failed to identify 60% of women with abnormal 2-h glucose levels. Screening women with previous GDM (and by analogy, other groups at high risk of diabetes) with a single fasting glucose has low sensitivity for the detection of abnormal glucose tolerance. Recent guidelines recommending this approach require reevaluation.
ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.
Authors: Rabensteiner D , Abrahamian H , Irsigler K , Hermann K M , Kiener H P , Mayer G , Kaider A , Prager R
Published: March 2007

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy
Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin.
Authors: Rissanen J , Markkanen A , Kärkkäinen P , Pihlajamäki J , Kekäläinen P , Mykkänen L , Kuusisto J , Karhapää P , Niskanen L , Laakso M
Published: March 2007

OBJECTIVE: To investigate the possible association of the variants in the nucleotide binding fold regions of the sulfonylurea receptor 1 (SUR1) gene with gestational diabetes mellitus (GDM), type 2 diabetes, and altered insulin secretion in Finnish subjects. RESEARCH DESIGN AND METHODS: The nucleotide binding fold regions of the SUR1 gene were amplified with polymerase chain reaction and screened by the single-strand conformational polymorphism analysis in 42 subjects with GDM and 40 subjects with type 2 diabetes. Detected variants were further investigated in 377 normoglycemic subjects by restriction fragment-length polymorphism analysis. The effect of the variants of the SUR1 gene on first-phase insulin secretion was studied in 295 normoglycemic subjects. RESULTS: In subjects with GDM or type 2 diabetes, one amino acid change (S1369A), four silent substitutions (R1273R, L829L, T759T, and K649K), and three intron variants were identified in the nucleotide binding fold regions of the SUR1 gene. A tagGCC allele of exon 16 splice acceptor site was more frequent in subjects with GDM (0.55 allele frequency, n = 42) and type 2 diabetes (0.60, n = 40) than in normoglycemic subjects (0.43, n = 377) (P1 = 0.024 and P2 = 0.009, respectively). Similarly, an AGG allele of the R1273R polymorphism was more common in subjects with GDM (0.87) and type 2 diabetes (0.87) than in normoglycemic subjects (0.74) (P1 = 0.009 and P2 = 0.001, respectively). However, the S1369A, R1273R, and cagGCC-->tagGCC variants of the SUR1 gene were not associated with altered first-phase insulin secretion in 295 normoglycemic subjects. CONCLUSIONS: These results suggest that a functional variant that contributes to the risk of GDM and type 2 diabetes may locate close to the SUR1 gene.
Association of hyperandrogenemia and hyperestrogenemia with type 2 diabetes in Hispanic postmenopausal women.
Authors: Phillips G B , Tuck C H , Jing T Y , Boden-Albala B , Lin I F , Dahodwala N , Sacco R L
Published: March 2007

OBJECTIVE: Accumulating evidence suggests that hyperandrogenemia may be a risk factor for coronary heart disease (CHD) in women. The present study was carried out to test the hypothesis that hyperandrogenemia is associated with type 2 diabetes in women and thus may contribute to the increased risk of CHD in women with type 2 diabetes. RESEARCH DESIGN AND METHODS: Sex hormones, sex hormone-binding globulin (SHBG), and risk factors for CHD were measured in 20 postmenopausal women with type 2 diabetes and in 29 control subjects. All of the diabetic and control subjects were Hispanic women aged >55 years who were not taking hormone replacement therapy lipid-lowering drugs, or insulin and who were otherwise randomly chosen from a cohort of stroke-free subjects from the Northern Manhattan Stroke Study RESULTS: Mean age, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood pressure, and smoking were not significantly different between cases and control subjects, but waist-to-hip ratio (WHR) was significantly higher in the diabetic subjects (P = 0.01). The mean levels of free testosterone (FT) (P = 0.01), dehydroepiandrosterone sulfate (P<0.04), and estradiol (P = 0.01) (controlled for WHR) were significantly higher in the diabetic subjects; with the statistical outliers removed, the testosterone (P = 0.05) and androstenedione (P = 0.002) levels (controlled for WHR) were also significantly higher in the diabetic subjects. The mean levels of estrone, cortisol, and SHBG were not significantly different. The results were similar in the 10 diabetic subjects treated with diet only Significant positive correlations (controlled for age and BMI) were observed between FT or testosterone and cholesterol, LDL cholesterol, and blood pressure. CONCLUSIONS: Postmenopausal Hispanic women with type 2 diabetes had both hyperandrogenemia and hyperestrogenemia, and testosterone or FT correlated positively with risk factors for CHD. Hyperandrogenemia may be a link between diabetes and CHD in women.
Dental and other health care visits among U.S. adults with diabetes.
Authors: Tomar S L , Lester A
Published: March 2007

OBJECTIVE: This study compared yearly dental visits of diabetic adults with those of nondiabetic adults. For adults with diabetes, we compared the frequency of past-year dental visits with past-year visits for diabetes care, dilated eye examinations, and foot examinations. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study using a sample of 105,718 dentate individuals aged > or =25 years, including 4,605 individuals with diabetes who participated in the 1995-1998 Behavioral Risk Factor Surveillance System in 38 states. RESULTS: Dentate adults (i.e., those with at least some natural teeth) with diabetes were less likely than those without diabetes to have seen a dentist within the preceding 12 months (65.8 vs. 73.1%, P = 0.0000). Adults with diabetes were less likely to have seen a dentist than to have seen a health care provider for diabetes care (86.3%); the percentage who saw a dentist was comparable with the percentage who had their feet examined (67.7%) or had a dilated eye examination (62.3%). The disparity in dental visits among racial or ethnic groups and among socioeconomic groups was greater than that for any other type of health care visit for subjects with diabetes. CONCLUSIONS: Promotion of oral health among diabetic patients may be necessary, particularly in Hispanic and African-American communities. Information on oral health complications should be included in clinical training programs. Oral and diabetes control programs in state health departments should collaborate to promote preventive dental services, and the oral examination should be listed as a component of continuous care in the American Diabetes Association's standards of medical care for diabetic patients.
Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy.
Authors: Garg A , Stray-Gundersen J , Parsons D , Bertocci L A
Published: March 2007

OBJECTIVE: Congenital generalized lipodystrophy (CGL) is an autosomal recessive genetic disorder characterized by almost complete absence of adipose tissue, muscular appearance, and severe insulin resistance since birth. We investigated whether insulin resistance in CGL patients is associated with abnormal muscle morphology and whether increased muscularity imparts increased muscle strength and exercise capacity RESEARCH DESIGN AND METHODS: We obtained quadriceps muscle biopsies to study muscle fiber types and capillary density in three African-American women (aged 17-20 years) with CGL. We also assessed quadriceps muscle strength, muscle metabolism, and maximal O2 consumption in the patients. RESULTS: Quadriceps muscle biopsies revealed a markedly higher percentage of type II (fast-twitch glycolytic) muscle fibers in patients with CGL versus sedentary young women (75-78 vs. 47-57%, respectively). The capillary-to-fiber ratio (2.7-3.0), however, was normal. Cross-sectional areas of type I (slow-twitch oxidative) (1,262-2,685 microm2) and type II (2,304-3,594 microm2) fibers were far below the normal values (3,811-4,310 and 3,115-4,193 microm2, respectively), suggesting muscle hyperplasia but not hypertrophy The quadriceps muscle strength, as measured by Cybex, was below average; the maximal O2 consumption (23-32 ml x kg(-1) x min(-1)) was also below average. 31P nuclear magnetic resonance spectroscopy of the forearm muscles revealed normal pH and metabolic responses to static and dynamic exercises. CONCLUSIONS: We conclude that insulin resistance in patients with CGL is associated with an increased proportion of type II muscle fibers but not reduced capillary density. Increased muscularity in CGL is due to muscle hyperplasia and is not associated with increased muscle strength.
Screening for type 2 diabetes.
Authors: Engelgau M M , Narayan K M , Herman W H
Published: March 2007

Definitive studies of the effectiveness of screening for type 2 diabetes are currently not available. RCTs would be the best means to assess effectiveness, but several barriers prevent these studies from being conducted. Prospective observational studies may characterize some of the benefits of screening by creating screened and unscreened groups for comparison. The availability of better data systems and health services research techniques will facilitate such comparisons. Unfortunately, the interpretation of the results of such studies is extremely problematic. Several screening tests have been evaluated. Risk assessment questionnaires have generally performed poorly as stand-alone tests. Screening with biochemical tests performs better. Venous and capillary glucose measurements may perform more favorably than urinary glucose or HbA(1c) measurements, and measuring postprandial glucose levels may have advantages over measuring fasting levels. However, performance of all screening tests is dependent on the cutoff point selected. Unfortunately, there are no well-defined and validated cutoff points to define positive tests. A two-stage screening test strategy may assist with a more efficient use of resources, although such approaches have not been rigorously tested. The optimal interval for screening is unknown. Even though periodic, targeted, and opportunistic screening within the existing health care system seems to offer the greatest yield and likelihood of appropriate follow-up and treatment, much of the reported experience with screening appears to be episodic poorly targeted community screening outside of the existing health care system. Statistical models have helped to answer some of the key questions concerning areas in which there is lack of empirical data. Current models need to be refined with new clinical and epidemiological information, such as the UKPDS results (200). In addition, future models need to include better information on the natural history of the preclinical phase of diabetes. Data from ongoing clinical trials of screening and treatment of impaired glucose tolerance, such as the Diabetes Prevention Program, may eventually offer more direct evidence for early detection and treatment of asymptomatic hyperglycemia (201). It will be important to use comprehensive cardiovascular disease modules that assess the conjoint influence of glucose and cardiovascular risk factor reduction, information on QOL, and refined economic evaluations using common outcome measures (cost per life-year or QALY gained) (11,178,202-204). Such studies should consider all of the costs associated with a comprehensive screening program, including, at a minimum, the direct costs of screening, diagnostic testing, and care for patients with diabetes detected through screening. Finally, combinations of screening tests and different screening intervals should be evaluated within economic studies to allow selection of the optimal approach within the financial and resource limitations of the health care system.
Preoperative triglycerides predict post-coronary artery bypass graft survival in diabetic patients: a sex analysis.
Authors: Sprecher D L , Pearce G L , Park E M , Pashkow F J , Hoogwerf B J
Published: March 2007

OBJECTIVE: Hypertriglyceridemia is commonly observed in association with diabetes. Despite cross-sectional studies and isolated longitudinal analyses in patients without coronary artery disease, the suggestion that triglyceride levels are relevant to subsequent cardiovascular events in the setting of diabetes remains controversial. This study evaluates the predictive value of serum triglyceride levels on mortality in post-coronary artery bypass graft (CABG) diabetic patients with subsequent analysis by sex. RESEARCH DESIGN AND METHODS: This longitudinal observational study involving a large metropolitan hospital consists of 1,172 diabetic post-CABG patients (792 men and 380 women) with lipid data collected between the years 1982 and 1992. Cox proportional hazards regression models were used to estimate the risk of mortality and cardiac events associated with triglyceride levels in the highest quartile (> 2.90 mmol/l for men and > 3.12 mmol/l for women). RESULTS: Elevated preoperative serum triglyceride values in post-CABG subjects with diabetes were correlated with increased overall mortality (hazard ratio [HR] 1.26, 95% CI 1.00-1.59). The greatest influence of triglyceride levels was observed on overall (1.89, 1.30-2.73) and event-free survival (1.49, 1.06-2.08) in women. High triglyceride values were also modestly related to risk of cardiac events in diabetic men (1.28, 0.99-1.66). CONCLUSIONS: These data suggest that increased preoperative triglyceride levels predict increased late mortality and cardiac event risk in diabetic post-CABG patients, more strongly in women than in men.
Lack of impact of low-dose acetylsalicylic acid on kidney function in type 1 diabetic patients with microalbuminuria.
Authors: Hansen H P , Gaede P H , Jensen B R , Parving H H
Published: March 2007

OBJECTIVE: High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients with microalbuminuria and macroalbuminuria. This effect may lead to an incorrect classification of albuminuria (normo-, micro-, and macroalbuminuria) and jeopardize the monitoring of antiproteinuric treatment (e.g., ACE inhibition). Whether similar difficulties exist using low-dose acetylsalicylic acid (ASA), now widely recommended for primary and secondary prevention of cardiovascular events in type 1 diabetic patients with micro- and macroalbuminuria, remains to be elucidated. RESEARCH DESIGN AND METHODS: We performed a randomized double-blind crossover trial in 17 type 1 diabetic patients with microalbuminuria (urinary AER 30-300 mg/24 h). Patients were given ASA (150 mg/daily) for 4 weeks followed by placebo for 4 weeks with at least a 2-week washout period in random order. At the end of each treatment period, AER (enzyme-linked immunosorbent assay), glomerular filtration rate (GFR) (plasma clearance of 51Cr-EDTA), blood pressure (BP) (Hawksley), and HbA1c (by high-performance liquid chromatography) were measured. Patients were advised to follow a normal diabetes diet without sodium restriction and received their usual antihypertensive treatment during the investigation. RESULTS: During the study (ASA vs. placebo), urinary AER (geometric mean 64 [95% CI 39-105] vs. 59 [40-87] mg/24 h), GFR (mean 106 [93-118] vs. 104 [90-117] ml x min(-1) x 1.73 m(-2)), systolic BP (mean 130 [119-141] vs. 130 [119-142] mmHg), diastolic BP (mean 71 [65-78] vs. 71 [64-78] mmHg), and HbA1c (mean 8.4% [8.0-9.0] vs. 8.5% [8.1-9.0]) remained unchanged. CONCLUSIONS: Treatment with 150 mg ASA daily does not have any impact on AER or GFR in type 1 diabetic patients with microalbuminuria. Consequently, primary and secondary prevention of cardiovascular events with low-dose ASA does not interfere with the classification of AER or monitoring of antiproteinuric treatment in such patients.
Mutations in the genes for hepatocyte nuclear factor (HNF)-1alpha, -4alpha, -1beta, and -3beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in Pima Indians.
Authors: Baier L J , Permana P A , Traurig M , Dobberfuhl A , Wiedrich C , Sutherland J , Thuillez P , Luczy-Bachman G , Hara M , Horikawa Y , Hinokio Y , Hanson R L , Bogardus C
Published: March 2007

OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODY can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset type 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS: The coding regions of the known MODY genes hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, HNF-1beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF-3beta and the dimerization cofactor of HNF-1, were sequenced in genomic DNA from Pima Indians. The primary "affected" study population consisted of 46 Pima Indians whose age at onset of type 2 diabetes was < or =20 years. DNA sequence variants identified in the affected group were then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 years old and had normal glucose tolerance. RESULTS: A total of 11 polymorphisms were detected in these genes. However, none of the polymorphisms differed in frequency among Pima Indians with an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS: Mutations in these known MODY or MODY candidate genes are not a common cause of early-onset diabetes in Pima Indians.
Development of a health status measure for older African-American women with type 2 diabetes.
Authors: Elasy T A , Samuel-Hodge C D , DeVellis R F , Skelly A H , Ammerman A S , Keyserling T C
Published: March 2007

OBJECTIVE: To develop a health status measure in older African-American women with type 2 diabetes. RESEARCH DESIGN AND METHODS: African-American women, age > or =40 years with type 2 diabetes, were recruited from central North Carolina to participate in three sequential phases: 1) Seven focus groups were convened and transcripts evaluated to generate questions and identify plausible domains; 2) Ten one-on-one cognitive response interviews were performed to ensure clarity and cultural appropriateness of the questions; and 3) 217 women participated in psychometric evaluation to establish the internal consistency and validity of the instrument. RESULTS: Three broad categories--mental, physical, and social well-being--captured important issues generated during the focus groups. "My diabetes" was added during the cognitive response interviews as a way of separating the impact of diabetes from coexisting issues that affect health status. The response option was changed from a six- to a four-point Likert scale to accommodate subject preference. Using principal components and subsequent promax rotation, we identified two hierarchical domains (mental and social well-being) and a physical symptom index. The internal consistency (Cronbach's alpha) of the mental and social well-being subscales are 0.83 and 0.93, respectively. A priori hypothesized correlations between subscales along with each subscale and glycated hemoglobin, diabetes duration, physical activity, and a perceived health competence scale helped establish the construct validity of the instrument. CONCLUSIONS: A culturally appropriate disease-specific health status measure for older African-American women with type 2 diabetes has been developed. We have established the internal consistency, construct validity, and factor analytic properties of the measure. This measure should prove useful for investigators who seek a health status instrument that addresses issues germane to African-American women with type 2 diabetes.
Prevalence and correlates of preventive care among adults with diabetes in Kansas.
Authors: Ahluwalia H K , Miller C E , Pickard S P , Mayo M S , Ahluwalia J S , Beckles G L
Published: March 2007

OBJECTIVE: To assess the prevalence and correlates of recommended preventive care among adults with diabetes in Kansas. RESEARCH DESIGN AND METHODS: A cross-sectional telephone survey was conducted among a sample of adults (> or = 18 years of age) with self-reported diabetes. Recommended preventive care was defined based on four criteria: number of health-care provider (HCP) visits per year (> or = 4 for insulin users and > or = 2 for nonusers), number of foot examinations per year (> or = 4 for insulin users and > or = 2 for nonusers), an annual dilated eye examination, and a blood pressure measurement in the past 6 months. RESULTS: The mean age of the 640 respondents was 61 years, 58% were women, and 86% were white. In the preceding year, 62% of respondents reported the appropriate number of visits to a HCP 27% the appropriate number of foot examinations, 65% an annual dilated eye examination, and 89% a blood pressure measurement in the preceding 6 months. Only 17% (95% CI 14-20) met all four criteria for recommended care. The adjusted odds of receiving recommended care were higher for males than for females (odds ratio [OR] 1.6; 95% CI 1.1-2.5), higher for people whose HCP scheduled follow-up appointments than for those who self-initiated follow-up (OR 2.7; 95% CI 1.6-4.8), and higher for former smokers than for current smokers (OR 3.1; 95% CI 1.6-6.9). CONCLUSIONS: Preventive care for people with diabetes is not being delivered in compliance with current guidelines, especially for women and current smokers. Scheduling follow-up visits for patients, targeting certain high-risk populations, and developing protocols to improve foot care may be effective in improving care.
Islet dysfunction in insulin resistance involves impaired insulin secretion and increased glucagon secretion in postmenopausal women with impaired glucose tolerance.
Authors: Larsson H , Ahrén B
Published: March 2007

OBJECTIVE: To characterize in detail the association between insulin sensitivity and islet function in relation to glucose tolerance in nondiabetic subjects. RESEARCH DESIGN AND METHODS: The study included 108 postmenopausal women, aged 57-59 years, with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) and measured glucose tolerance (World Health Organization, 75 g glucose), insulin sensitivity (euglycemic-hyperinsulinemic clamp), and islet function (the 2-5 min insulin responses [AIR] and glucagon [AGR] responses to 5 g intravenous arginine at fasting, 14 and >25 mmol/l glucose levels). The product of insulin sensitivity and secretion was calculated (disposition index [DI]) and used to study the relationship between the two parameters. RESULTS: Insulin sensitivity and insulin secretion were highly inversely correlated in a hyperbolic manner (r > 0.64, P < 0.001) in women with NGT (n = 71). Women with IGT (n = 37) had reduced insulin sensitivity compared with women with NGT (P = 0.011). The AIRs were not appropriately increased in relation to the reduced insulin sensitivity in the IGT women, demonstrated as reduced DI in IGT compared with NGT (P < 0.001). Further, women with IGT had an increased AGR (P < 0.001) and a reduced glucose inhibition of glucagon secretion (slopeAGR, P = 0.014) compared with women with NGT. In a multivariate regression model including all of the 108 women, 2-h glucose was independently determined by the DI, the AGR, and the slopeAGR (r = 0.63, P < 0.001). CONCLUSIONS: We have shown that both the individual ability to adapt insulin secretion to the ambient insulin sensitivity and the level of glucagon secretion are important parameters for maintenance of NGT. Therefore, islet dysfunction in IGT involves low insulin and high glucagon secretion, which present potential targets for correcting impaired glycemia.