bluuebunny/crossref_metadata_2025 huggingface dataset:
High Blood Glucose Concentration Is a Risk Factor for Mortality in Middle-Aged Nondiabetic Men: 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study
Authors: Balkau Beverley , Shipley Martin , Jarrett R John , Pyörälä Kalevi , Pyörälä Marja , Forhan Anne , Eschwège Eveline
Published: March 2007

OBJECTIVE

To assess the association between high but nondiabetic blood glucose levels and the risk of death from all causes, coronary heart disease (CHD), cardiovascular disease, and neoplasms.

RESEARCH DESIGN AND METHODS

We studied the 20-year mortality of non-diabetic, working men, age 44–55 years, in three European cohorts known as the Whitehall Study (n = 10,025), the Paris Prospective Study (n = 6,629), and the Helsinki Policeman Study (n = 631). These men were identified by their 2-h glucose levels following an oral glucose tolerance test and by the absence of a prior diagnosis of diabetes. As the protocol for the oral glucose tolerance test and methods for measuring glucose differed between studies, mortality was analyzed according to the percentiles of the 2-h and fasting glucose distributions, using the Cox's proportional hazards model.

RESULTS

Men in the upper 20% of the 2-h glucose distributions and those in the upper 2.5% for fasting glucose had a significantly higher risk of all-cause mortality in comparison with men in the lower 80% of these distributions, with age-adjusted hazard ratios of 1.6 (95% CI 1.4–1.9) and 2.0 (1.6–2.6) for the upper 2.5%. For death from cardiovascular and CHD, men in the upper 2.5% of the 2-h and fasting glucose distributions were at higher risk, with age-adjusted hazard ratios for CHD of 1.8 (1.4–2.4) and 2.7 (1.7–4.4), respectively.

CONCLUSIONS

If early intervention aimed at lowering blood glucose concentrations can be shown to reduce mortality, it may be justified to lower the levels of both 2-h and fasting glucose, which define diabetes.
Longitudinal Changes in Pancreatic β-Cell Function and Metabolic Clearance Rate of Insulin in Pregnant Women With Normal and Abnormal Glucose Tolerance
Authors: Catalano Patrick M , Drago Noreen M , Amini Saeid B
Published: March 2007

OBJECTIVE

To evaluate basal pancreatic β-cell secretion and suppression during infused insulin and the metabolic clearance rate of insulin in women with normal and abnormal glucose tolerance prior to conception and during pregnancy.

RESEARCH DESIGN AND METHODS

Seven women with normal glucose tolerance and nine women with abnormal glucose tolerance during gestation were evaluated prior to conception, in early (12–14 weeks) and late (34–36 weeks) gestation. Basal insulin and C-peptide were measured after an 11-h fast and during the last 40 min of a 2-h hyperinsulinemic-euglycemic clamp at 40 mU·m−2·m−1. Suppression of basal C-peptide was calculated as the steady-state C-peptide/basal C-peptide. The metabolic clearance rate of insulin was calculated by dividing the insulin infusion rate by the steady-state insulin concentration, which was corrected for residual β-cell secretion.

RESULTS

No significant differences were noted in the following parameters between women with normal and abnormal glucose tolerance with advancing gestation: increase in basal insulin (P = 0.20) and C-peptide (P = 0.12), ability of infused insulin to decrease basal C-peptide concentration (P = 0.22), and metabolic clearance rate of insulin (P = 0.76). There was a significant 65% increase in both basal insulin (P = 0.0005) and C-peptide (P = 0.0002) concentrations in all subjects with advancing gestation. There was a significant (P = 0.0001) decrease in the ability of the infused insulin to decrease basal C-peptide concentration. C-peptide as a percentage of the basal was 64% before conception, 74% in early pregnancy, and 108% in late pregnancy. The metabolic clearance rate of insulin significantly (P = 0.0005) increased with advancing gestation: pregravid 442 ml·m−2 · min−1, early pregnancy 514 ml·m−2· min−1, and 526 ml·m−2 · min−1 in late pregnancy.

CONCLUSIONS

Pregnancy is accompanied by progressive alterations in insulin kinetics, which are partly responsible for the hyperinsulinemia of this condition. These alterations are more likely a homeostatic response to the increased physiological insulin resistance of pregnancy.
Normalization of Plasma Lipid Peroxides, Monocyte Adhesion, and Tumor Necrosis Factor-α Production in NIDDM Patients After Gliclazide Treatment
Authors: Desfaits Anne-Cécile , Serri Omar , Renier Geneviève
Published: March 2007

OBJECTIVE

To evaluate the effect of gliclazide administration to NIDDM patients on 1) monocyte adhesion to cultured endothelial cells, 2) plasma cytokine and lipid peroxide levels, and 3) monocyte cytokine production.

RESEARCH DESIGN AND METHODS

Poorly controlled glyburide-treated diabetic patients (n = 8) and healthy control subjects (n = 8) were recruited. At the beginning of the study, glyburide was replaced by an equivalent hypoglycemic dose of gliclazide. Serum and monocytes were isolated from blood obtained from control and diabetic subjects before and after 3 months of treatment with gliclazide.

RESULTS

Plasma lipid peroxide levels and monocyte adhesion to endothelial cells are enhanced in NIDDM patients, and gliclazide administration totally reverses these abnormalities. Before gliclazide treatment, serum levels of cytokines did not differ in the control and the diabetic groups, with the exception of an enhancement of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL)-6 in NIDDM subjects. Basal and lipopolysaccharide (LPS)-stimulated monocyte production of interleukin-1β, IL-6, and IL-8 did not differ between the two groups. Furthermore, basal monocyte production of TNF-α was similar in the control and the diabetic groups, whereas a marked increase in the LPS-stimulated monocyte production of TNF-α was observed in the NIDDM group. Gliclazide treatment lowered LPS-stimulated TNF-α production by diabetic monocytes to levels similar to those observed in control subjects.

CONCLUSIONS

Gliclazide administration to NIDDM patients inhibits the increased adhesiveness of diabetic monocytes to endothelial cells and reduces the production of TNF-α by these cells. These results suggest that treatment of NIDDM subjects with gliclazide may be beneficial in the prevention of atherosclerosis associated with NIDDM.
Diabetes in Urban African-Americans. VI. Utility of Fasting or Random Glucose in Identifying Poor Glycemic Control
Authors: El-Kebbi Imad M , Ziemer David C , Gallina Daniel L , Phillips Lawrence S
Published: March 2007

OBJECTIVE

African-Americans have an increased prevalence of both diabetes and diabetes complications, creating an imperative for improved metabolic control. Because American Diabetes Association guidelines recommend that action be taken when HbA1c is >8.0', but access to rapid-turnaround HbA1c assays remains limited, we tested the utility of fasting and random plasma glucose cutoffs as indicators of HbA1c >8.0%.

RESEARCH DESIGN AND METHODS

Using receiver operating characteristics (ROC) analysis, we evaluated the sensitivity, specificity, and predictive value of fasting and random plasma glucose measurements in identifying an HbA1c >8.0% (fasting n = 974, random n = 552). The population studied was predominantly African-American, middle-aged, and noninsulin-dependent.

RESULTS

Fasting plasma glucose was a significant indicator of HbA1c >8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.87, 0.90, 0.87, and 0.84, respectively (all P < 0.0001). A fasting plasma glucose cutoff of >9.2 mmol/1 (165 mg/dl) provided a sensitivity of 80% and a specificity of 83% for the whole group and a 77% positive predictive value. Random plasma glucose was also a good indicator of HbA1c >8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.85, 0.91, 0.85, and 0.77, respectively (all P < 0.0001). A cutoff >9.8 mmol/1 (177 mg/dl) provided a sensitivity of 78% and a specificity of 77% for the whole group and a 78% positive predictive value. Overall, a plasma glucose >11.1 mmol/1 (200 mg/dl) identified an HbA1c >8.0% with a predictive value of ∼90% if done while fasting and a predictive value of ∼80–85% if random. The utility of both fasting and random plasma glucose cutoffs was subsequently confirmed in a prospective study of another 2,309 and 1,396 patients, respectively.

CONCLUSIONS

Although glucose levels cannot replace HbA1c determinations, measurement of fasting or random plasma glucose may be used during a clinic visit to identify poorly controlled type 2 patients with reasonable certainty and allow timely patient education and therapeutic intervention.
Prevalence of Glucose Intolerance Among Native Hawaiians in Two Rural Communities
Authors: Grandinetti Andrew , Chang Healani K , Mau Marjorie K , Curb J David , Kinney Everett K , Sagum Rebecca , Arakaki Richard F
Published: March 2007

OBJECTIVE

To estimate prevalence of type 2 diabetes and impaired glucose tolerance (IGT) among a population of native Hawaiians in two rural communities.

RESEARCH DESIGN AND METHODS

Prevalence of glucose intolerance was assessed in two rural communities by history (confirmed by record review) or with a 75-g oral glucose tolerance test according to World Health Organization criteria. Anthropometric and demographic data were also obtained. A short survey was used to estimate the prevalence of known diabetes among nonparticipants. Prevalence rates were adjusted using the standard world population of Segi.

RESULTS

A total of 574 native Hawaiians age ≥30 years participated. The crude prevalence of IGT and type 2 diabetes were 15.5 and 20.4%, respectively. Only IGT prevalence was significantly higher (P = 0.03) among women (18.7%) than among men (10.9%). Prevalence of glucose intolerance was significantly associated with BM1, waist circumference, and waistto-hip ratio (WHR). After adjusting for age and BMI, waist circumference and WHR were significantly and independently associated with type 2 diabetes prevalence only among women. Prevalence of type 2 diabetes was not significantly associated with the percentage of Hawaiian ancestry after adjusting for age.

CONCLUSIONS

This study observed a high prevalence of glucose intolerance associated with being overweight among native Hawaiians. Age-adjusted type 2 diabetes prevalence was four times higher than among the U.S. National Health and Nutrition Examination Survey (NHANES) II population. Prevalence was high despite high rates of admixture with other ethnic groups of Hawaii, suggesting that these other Asian and Pacific Island populations share similar susceptibility to type 2 diabetes risk.
Diabetes and Impaired Glucose Tolerance in Three Alaskan Eskimo Populations: The Alaska-Siberia Project
Authors: Ebbesson Sven O K , Schraer Cynthia D , Risica Patricia M , Adler Amanda I , Ebbesson Lars , Mayer Ann Marie , Shubnikof Eugene V , Yeh Jeunliang , Go Oskar T , Robbins David C
Published: March 2007

OBJECTIVE

The objectives of this study were to determine the prevalence of diabetes and impaired glucose tolerance (IGT) in three Alaskan Eskimo populations, using standardized diagnostic criteria, and to evaluate family history and obesity as risk factors.

RESEARCH DESIGN AND METHODS

This cross-sectional study involved men and women ≥25 years of age from three Eskimo ethnic groups (Siberian Yupik, Central Yupik, and Inupiat) residing in northwestern Alaska. Glucose tolerance status was denned by World Health Organization criteria and was based on a 75-g oral glucose tolerance test. Data on age, family history of diabetes, and degree of Eskimo ancestry were obtained from a personal interview. Obesity was assessed using BMI.

RESULTS

A total of 454 of 899 (50.5%) eligible participants were examined for diabetic status (239 Siberian Yupik, 106 Central Yupik, and 109 Inupiat participants). The prevalence of diabetes was more than twice as high among the Siberian Yupik (9.6%) as among the Central Yupik (2.8%) and Inupiat participants (3.7%). Diabetes was more prevalent in women than men (8.8 vs. 4.2%). IGT was found in an additional 11.7% of the women and 4.7% of the men. The combined prevalence of diabetes and IGT in the population ≥55 years of age was 30.4% (diabetes 12.0%, IGT 18.4%). Of the people identified with diabetes, 47% had not been previously diagnosed. Age-specific prevalences were similar to those found in U.S. whites in the National Health and Nutrition Examination Survey II. After adjustment for age, family history of diabetes was associated with diabetes in study participants with an odds ratio of 4.4, while obesity was associated with diabetes with an odds ratio of 2.6.

CONCLUSIONS

These prevalences of diabetes are the highest yet reported among Eskimo populations. Obesity and family history of diabetes are associated with increased odds of developing diabetes. These data underscore the need to further examine risk factors and to design effective interventions.
Low-Intensity Laser Irradiation Improves Skin Circulation in Patients With Diabetic Microangiopathy
Authors: Schindl Andreas , Schindl Martin , Schön Heidemarie , Knobler Robert , Havelec Liselotte , Schindl Liesbeth
Published: March 2007

OBJECTIVE

Diabetic foot problems due to angiopathy and neuropathy account for 50% of all nontraumatic amputations and constitute a significant economic burden to society. Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation. We investigated the influence of low-intensity laser irradiation by means of infrared thermography on skin blood circulation in diabetic patients with diabetic microangiopathy.

RESEARCH DESIGN AND METHODS

Thirty consecutive patients with diabetic ulcers or gangrenes and elevated levels of glycosylated hemoglobin were randomized by blocks of two to receive either a single low-intensity laser irradiation with an energy density of 30 J/cm2 or a sham irradiation over both forefoot regions in a double-blind placebo-controlled clinical study. Skin blood circulation as indicated by temperature recordings over the forefoot region was detected by infrared thermography.

RESULTS

After a single transcutaneous low-intensity laser irradiation, a statistically significant rise in skin temperature was noted (P < 0.001 by ANOVA for repeated measurements), whereas in the sham-irradiated control group, a slight but significant drop in temperature (P < 0.001) was found. Subsequently performed contrasts for comparison of measurements before and after irradiation revealed significant temperature increases at 20 min of irradiation time (P < 0.001), at the end of the irradiation (P < 0.001), and 15 min after stopping the irradiation (P < 0.001). In the sham-irradiated feet, the drop in local skin temperature was not significant at 20 min (P = 0.1), but reached significance at the end of the sham-irradiation procedure (P < 0.001) and 15 min after the end of sham irradiation (P < 0.001).

CONCLUSIONS

The data from this first randomized double-blind placebo-controlled clinical trial demonstrate an increase in skin microcirculation due to athermic laser irradiation in patients with diabetic microangiopathy.
Cardiovascular Outcomes in Type 2 Diabetes: A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study
Authors: Elkeles Robert S , Diamond Judith R , Poulter Clare , Dhanjil Surinder , Nicolaides Andrew N , Mahmood Shahid , Richmond William , Mather Hugh , Sharp Patrick , Feher Michael D ,   SENDCAP Study Group
Published: March 2007

OBJECTIVE

To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes.

RESEARCH DESIGN AND METHODS

There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)—clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)—were recorded.

RESULTS

Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (−32 vs. 4%, P = 0.001), total cholesterol (−7 vs. −0.3%, P = 0.004), and total−to-HDL cholesterol ratio (−12 vs. −0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. −2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (−18 vs. −6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction.

CONCLUSIONS

Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of “definite CHD events” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.
Plasma Fibrinogen: A New Factor of the Metabolic Syndrome: A population-based study
Authors: Imperatore Gluseppina , Riccardi Gabriele , Iovine Ciro , Rivellese Angela A , Vaccaro Olga
Published: March 2007

OBJECTIVE

To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome.

RESEARCH DESIGN AND METHODS

A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35–64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome.

RESULTS

Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 ± 1.9 vs. 300.2 ± 3.0 mg/dl, mean ± SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as ≥350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen.

CONCLUSIONS

The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.
Effect of Meal Dilution on the Postprandial Glycemic Response: Implications for glycemic testing
Authors: Sievenpiper John L , Vuksan Vladimir , Wong Evelyn YY , Mendelson Rena A , Bruce-Thompson Charles
Published: March 2007

OBJECTIVE

To investigate the effect of varying the volume of sugar meals on the postprandial glycemic response (PGR).

RESEARCH DESIGN AND METHODS

On six separate occasions, after an overnight fast, blood glucose concentrations were measured in eight healthy subjects (34 ± 4 years of age, BMI 22.9 ± 0.9 kg/m2) after the consumption of 25 g glucose, sucrose, or fructose dissolved in either 200 or 600 ml of water. Blood was obtained at fasting and then at times 15, 30, 45, 60, and 90 min after the start of the test meal.

RESULTS

PGR was found to be influenced by carbohydrate type (P < 0.001). Mean response areas (min · mmol · l−1) to the three sugars were statistically different (P <0.05). Glucose had the highest response area (90.0 ± 8.1), followed by sucrose (61.3 ± 5.0) and then fructose (14.7 ± 2.8). Independent of this effect, PGR was also found to be influenced by volume dose (P < 0.01). By tripling meal volume from 200 to 600 ml, PGR areas were significantly increased for all three sugars, glucose (79.3 ± 10.3 vs. 100.8 ± 12.0, P = 0.035), sucrose (52.6 ± 5.5 vs. 70 ± 7.4, P = 0.0094), and fructose (11.0 ± 3.8 vs. 18.4 ± 3.9, P = 0.012). Where the effects of time (P < 0.05) and dose (P < 0.05) were determined to be independent (interaction nonsignificant) for all three sugars, this increase in volume also significantly increased glycemic concentrations at 15 min, for glucose (P = 0.033) and sucrose (P = 0.026), suggesting that changes in gastric emptying time may be a mechanism of action.

CONCLUSIONS

Varying the volume of liquid sugar meals alters PGR.Understanding this concept may help to reduce variability both in the glycemic testing of foods and oral glucose tolerance testing.
Moderate Intake of n-3 Fatty Acids for 2 Months Has No Detrimental Effect on Glucose Metabolism and Could Ameliorate the Lipid Profile in Type 2 Diabetic Men: Results of a controlled study
Authors: Luo Jing , Rizkalla Salwa W , Vidal Hubert , Oppert Jean-Michel , Colas Claude , Boussairi Abdelghani , Guerre-Millo Michele , Chapuis Anne-Sophie , Chevalier Annie , Durand Georges , Slama Gérard
Published: March 2007

OBJECTIVE

To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue.

RESEARCH DESIGN AND METHODS

A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2- month washout interval, in a double-blind crossover design.

RESULTS

For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue.

CONCLUSIONS

A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol- lowering capacities.
Prospective Study of Serum γ-Glutamyltransferase and Risk of NIDDM
Authors: Perry Ivan J , Wannamethee S Goya , Shaper A Gerald
Published: March 2007

OBJECTIVE

Serum γ-glutamyltransferase (GGT) levels are raised inobese individuals, and a particularly strong association with central obesity has been described. We hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. To test this hypothesis, we examined the association between GGT levels and risk of NIDDM.

RESEARCH DESIGN AND METHODS

We carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40–59 years) followed for a mean of 12.8 years (range 11.5–13.0). The men were randomly selected from general practice lists in 24 British towns. Cases of NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records.

RESULTS

A total of 194 men developed NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% Cl]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3–22.6] vs. 15.3 U/l [15.0–15.6], P < 0.0001). There was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5–12.9) relative to the bottom fifth (trend P < 0.0001). This association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0–11.8], trend P < 0.0001]).

CONCLUSIONS

These findings suggest that a raised serum GGT levelis an independent risk factor for NIDDM. Serum GGT level may be a simple andreliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance.
Diabetes and Lower-Limb Amputations in the Community: A retrospective cohort study
Authors: Morris Andrew D , McAlpine Ritchie , Steinke Douglas , Boyle Douglas IR , Ebrahim Abdul-Rahim , Vasudev Naveen , Stewart Colin PU , Jung Roland T , Leese Graham P , MacDonald Thomas M , Newton Ray W ,   For the DARTS/MEMO Collaboration
Published: March 2007

OBJECTIVE

There are few U.K. data on the incidence rates of amputation in diabetic subjects compared with the nondiabetic population.

RESEARCH DESIGN AND METHODS

We performed a historical cohort study of first lower-extremity amputations based in Tayside, Scotland (population 364,880) from 1 January 1993 to 31 December 1994. The Diabetes Audit and Research in Tayside Scotland (DARTS) database was used to identify a prevalence cohort of 7,079 diabetic patients on 1 January 1993. We estimated age-specific and standardized incidence rates of lower-limb amputations in the diabetic and nondiabetic cohorts. Results were compared with a previous study that evaluated lower-extremity amputations in diabetic patients in Tayside in 1980–1982.

RESULTS

There were 221 subjects who underwent a total of 258 nontraumatic amputations. Of the 221 subjects, 60 (27%) patients were diabetic (93% NIDDM), and 63% were first amputations. The median duration of diabetes was 6 years (range: newly diagnosed to 41 years). Nonhealing ulceration (31%) and gangrene (29%) were the two main indications for amputation in the diabetic subjects. Of the 161 nondiabetic subjects, 140 (80%) underwent first amputations. The adjusted incidences in the diabetic and nondiabetic groups were 248 and 20 per 100,000 person-years, respectively. Tayside patients with diabetes thus had a 12.3-fold risk of an amputation compared with nondiabetic residents (95% Cl 8.6–17.5). The estimated proportion of diabetic patients in the population rose from 0.81% in 1980–1982 to 1.94% in 1993–1994, whereas the absolute rate of amputation in diabetic subjects was unchanged from that in 1980–1982.

CONCLUSIONS

These population-based U.K. amputation data are similar to amputation rates in the U.S. Amputation rates appear to have decreased significantly since 1980–1982. The impact of diabetes education and prevention programs that target the processes leading to amputation can now be evaluated.
Adaptation of the Dartmouth COOP Charts for Use Among American Indian People With Diabetes
Authors: Gilliland Susan S , Willmer Adisa J , McCalman Raylene , Davis Sally M , Hickey Martin E , Perez Georgia E , Owen Charles L , Carter Janette S
Published: March 2007

OBJECTIVE

To adapt the Dartmouth COOP Charts for use among American Indians with diabetes and to evaluate the operating characteristics of the adapted charts because measures of health status have not been evaluated for use among American Indians with diabetes.

RESEARCH DESIGN AND METHODS

American Indian adults participated in focus group conferences to adapt and review the Dartmouth COOP Charts for use in American Indian communities. American Indian participants with diabetes were interviewed and administered the adapted charts. The operating characteristics of the charts were evaluated by measuring internal and external consistency, reliability, and acceptability.

RESULTS

Some of the wording and pictures were considered to be offensive and culturally inappropriate in American Indian communities. The adapted charts showed internal consistency in a comparison of interchart variables.

CONCLUSIONS

The adapted Dartmouth COOP Charts are more culturally acceptable than the original charts and appear to measure constructs adequately.
Changes in Amylin and Amylin-Like Peptide Concentrations ana (β-Cell Function in Response to Sulfonylurea or Insulin Therapy in NIDDM
Authors: Rachman Jonathan , Payne Martin J , Levy Jonathan C , Barrow Beryl A , Holman Rury R , Turner Robert C
Published: March 2007

OBJECTIVE

Amylin, a secretory peptide of fi-cells, is the constituent peptide of islet amyloid, which is characteristic of NIDDM, and changes in amylin secretion in response to therapies may influence the rate of production of islet amyloid. The primary objective of this study was to determine whether therapy with sulfonylurea or basal insulin in NIDDM would alter amylin secretion in a way that might affect the formation of islet amyloid.

RESEARCH DESIGN AND METHODS

In a randomized crossover design, eight subjects with NIDDM underwent diree 8-week periods of therapy with diet alone, sulfonylurea, or exogenous basal insulin, with evaluation of amylin, amylin-like peptide (ALP), and glucose and C-peptide concentrations, both during fasting and after a standard breakfast. Changes in (β-cell function (%β) were assessed, in the basal state by homeostasis model assessment (HOMA) and in the stimulated state by hyperglycemic clamps. Seven nondiabetic control subjects each underwent a meal profile and hyperglycemic clamp.

RESULTS

Both sulfonylurea and insulin therapy reduced basal glucose concentrations compared with diet alone, but neither reduced the increased postprandial glucose increments. Both sulfonylurea and insulin therapy increased basal %β, assessed by HOMA, but only sulfonylurea increased the second-phase C-peptide responses to the hyperglycemic clamp. Sulfonylurea increased time-averaged mean postprandial amylin and ALP concentrations compared with diet alone (geometric mean [1-SD range] for amylin, 4.9 [2.0–11.8] vs. 3.0 [1.4–6.2] pmol/1, P = 0.003; for ALP, 16.4 [8.5–31.7] vs. 10.1 [4.9–20.8] pmol/1, P = 0.001). Insulin therapy reduced basal ALP concentrations compared with diet alone (2.9 [1.5–5.6] vs. 6.0 [2.6–13.6] pmol/1, P = 0.03), but had no effect on postprandial concentrations of amylin (3.0 [1.3–6.5] pmol/1) or ALP (10.0 [5.5–18.1] pmol/1).

CONCLUSIONS

By increasing postprandial concentrations of the constituent peptides of islet amyloid, sulfonylurea therapy might increase the rate of deposition of islet amyloid and thereby accelerate the decline of %β in NIDDM, compared with diet therapy alone.
Absence of Association Between Genetic Variation of the β3-Adrenercjic Receptor and Metabolic Pnenotypes in Oji-Cree
Authors: Hegele Robert A , Harris Stewart B , Hanley Anthony JG , Azouz Husain , Connelly Philip W , Zinman Bernard
Published: March 2007

OBJECTIVE

To assess the association between the common missense variant, Y64R, in the gene encoding the β3-adrenergic receptor, ADRB3, and intermediate phenotypes related to obesity and NIDDM in Canadian Oji-Cree.

RESEARCH DESIGN AND METHODS

We determined genotypes of the ADRB3 Y64R polymorphism in 508 clinically and biochemically well-characterized adult Oji-Cree, of whom 115 had NIDDM. We tested for associations with multivariate analysis of variance.

RESULTS

We found the ADRB3 R64 allele frequency to be 0.40 in this population, which is the highest yet observed in a human population. Furthermore, 15% of subjects were R64/R64 homozygotes, compared with a virtual absence of homozygotes in European study samples. However, we found no statistically significant associations of the ADRB3 Y64R genotype either with the presence of NIDDM, with indexes of obesity, or with intermediate quantitative biochemical traits related to NIDDM.

CONCLUSIONS

Despite the very high frequency of the ADRB3 R64 allele in this sample of aboriginal people, it was not associated with any metabolic phenotype. This suggests that the ADRB3 R64 allele is probably not a major determinant of obesity or NIDDM in these aboriginal Canadians.
High Prevalence of Diabetes in Bahrainis: Associations with ethnicity and raised plasma cholesterol
Authors: Al-Mahroos Faisal , McKeigue Paul M
Published: March 2007

OBJECTIVE

To determine prevalence of diabetes and associated risk factors in the population of Bahrain.

RESEARCH DESIGN AND METHODS

A cross-sectional study of 2,128 Bahrainis aged 40–69 years was conducted.

RESULTS

Age-standardized prevalence of diabetes was 25% in Jaafari Arabs, 48% in Sunni Arabs, and 23% in Iranians. In multivariate analyses, positive family history of diabetes, low educational status, waist girth, plasma cholesterol, and, in women, postmenopausal status were independently associated with diabetes. Adjusting for these factors did not account for the difference in prevalence between Jaafari and Sunni Arabs. There was no association between diabetes and parental consanguinity. Mean plasma cholesterol was 0.5 mmol/l higher in diabetic than in normoglycemic participants, 0.5 mmol/l higher in Sunni than in Jaafari Arabs, and, excluding diabetic individuals, 0.2 mmol/l higher in those with a positive family history of diabetes than in those with a negative family history. Although 28% of participants had BMI ≥ 30 kg/m2, only 42% of these obese individuals rated themselves as overweight. In men, obesity was inversely related to physical activity at work. In women, obesity was associated with high parity and inversely associated with employment outside the home.

CONCLUSIONS

The high rates of diabetes in Bahrain and other Arabian Peninsula populations appear to be part of a familial syndrome that includes raised plasma cholesterol levels. Risk is related to ethnic origin but not to parental consanguinity. Despite the high rates of diabetes, obesity is still perceived as a desirable attribute in this population.
Multicenter Study of the Incidence of and Predictive Risk Factors for Diabetic Neuropathic Foot Ulceration
Authors: Abbott Caroline A , Vileikyte Loretta , Williamson Sheila , Carrington Anne L , Boulton Andrew JM
Published: March 2007

OBJECTIVE

To investigate longitudinally prognostic factors for foot ulceration in a large population of diabetic patients with established neuropathy.

RESEARCH DESIGN AND METHODS

A double-blind multicenter study of a potential new agent for diabetic neuropathy provided the opportunity for this 1-year investigation since intervention demonstrated no efficacy in the condition. A total of 1,035 patients with N1DDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe ≥25 V in at least one foot and ≤50 V in both feet, normal peripheral circulation, and no previous foot ulceration. VPT and clinical components of the Michigan diabetic polyneuropathy (DPN) score were assessed at baseline and subsequent visits.

RESULTS

After 1 year, the incidence of first foot ulcers for the total population was 7.2%. Neuropathy parameters were the same between the treatment and placebo groups at baseline and were unchanged at 1 year; therefore, baseline data were combined for multiple regression analysis. VPT, age, and Michigan DPN scores for muscle strength and reflexes were significant independent predictors for first foot ulceration (P < 0.01). For each 1-U increase in VPT values at baseline, the hazard of the first foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength and reflex components of the Michigan DPN scores, the hazard of the first foot ulcer increased by 5.0%.

CONCLUSIONS

Tests of VPT and Michigan DPN scores for muscle strength and reflexes are useful clinical predictors for foot ulceration in diabetic patients with established neuropathy. The rate of subsequent ulceration in the following year was alarmingly high, however, despite standardized foot care education at baseline and regular follow-up visits.
Asp905Tyr Polymorphism of the Gene for the Skeletal Muscle-Specific Glycogen-Targeting Subunit of Protein Phosphatase 1 in NIDDM
Authors: Shen Gong-Qing , Ikegami Hiroshi , Kawaguchi Yoshihiko , Fujisawa Tomomi , Hamada Yoichi , Ueda Hironori , Shintani Maki , Nojima Koji , Kawabata Yumiko , Yamada Kazunori , Babaya Naru , Ogihara Toshio
Published: March 2007

OBJECTIVE

To clarify the contribution of the Asp905Tyr polymorphism of the musclespecific glycogen-targeting subunit of protein phosphatase 1 (PP1G) to insulin resistance and related diseases.

RESEARCH DESIGN AND METHODS

We investigated the Asp905Tyr polymorphism of the PPP1R3 gene, which encodes the muscle-specific glycogen-targeting subunit of PP1G, in 259 Japanese patients with NIDDM and 194 healthy control subjects.

RESULTS

No significant difference was found in the genotype distribution between NIDDM patients (n = 259; Asp/Asp = 0.10, Asp/Tyr = 0.44, Tyr/Tyr = 0.46) and healthy control subjects (n = 194; Asp/Asp = 0.13, Asp/Tyr = 0.37, Tyr/Tyr = 0.50) or between patient groups subdivided by the mode of treatment: NIDDM patients with insulin therapy (Asp/Asp = 0.14, Asp/Tyr = 0.46, Tyr/Tyr = 0.40) and those without insulin therapy (Asp/Asp = 0.07, Asp/Tyr = 0.43, Tyr/Tyr = 0.50). However, NIDDM patients with the Tyr allele, which was previously reported to be associated with insulin resistance, tended to have lower BMIs than those without this allele (Asp/Asp: 24.5 ±1.1 kg/m2, Asp/Tyr: 22.6 ± 0.4 kg/m2, Tyr/Tyr: 22.8 + 0.3 kg/m2, P = 0.06 by analysis of variance).

CONCLUSIONS

These data suggest that the Asp905Tyr polymorphism of the PPP1R3 gene is not associated with NIDDM or high BMI, both of which are known to be insulin-resistant states, in the Japanese population.
Diabetes in the African-American Medicare Population: Morbidity, quality of care, and resource utilization
Authors: Chin Marshall H , Zhang James X , Merrell Katie
Published: March 2007

OBJECTIVE

To determine whether African-American Medicare recipients with diabetes are at increased risk for morbidity, poor quality of care, and high resource utilization.

RESEARCH DESIGN AND METHODS

We analyzed 1,376 patients with diabetes who were ≥65 years of age and in the 1993 Medicare Current Beneficiary Survey. Morbidity measures were the Katz Index of Activities of Daily Living, Instrumental Activities of Daily Living, overall health perception, Charlson Comorbidity Index score, and diabetic complications. Quality of care standards were glycosylated hemoglobin measurements, ophthalmological visits, lipid testing, mammography, influenza vaccination, readmission within 30 days of hospital discharge, and outpatient visits within 4 weeks of hospital discharge. We stratified Medicare reimbursement by type of service and adjusted for sex, education, and age in multivariable analyses.

RESULTS

Compared with white patients, African-American patients had worse health perception and lower quality of care. They were more likely to visit the emergency department and had fewer physician visits per year. African-Americans had higher reimbursement for home health services, but total reimbursement was similar after case-mix adjustment.

CONCLUSIONS

Improved access to preventive care for older African-Americans with diabetes may improve health perception and use of the emergency department. The potential effect on total reimbursement is unclear. Future policy interventions to improve quality of care among Medicare patients with diabetes should especially target African-Americans.
Direct Medical Costs of Complications Resulting From Type 2 Diabetes in Hie U.S.
Authors: O'Brien Judith A , Shomphe Lori A , Kavanagh Patricia L , Raggio Gabriel , Caro J Jaime
Published: March 2007

OBJECTIVE

To estimate direct medical costs of managing the complications of type 2 diabetes.

RESEARCH DESIGN AND METHODS

Costs were estimated for 15 diabetic complications by applying unit costs to typical resource-use profiles. Resource use and unit costs were estimated from many sources, including acute care discharge databases, clinical guidelines, government reports, fee schedules, and peer-reviewed literature. For each complication, the event costs are those associated with resource use that is specific to the acute episode and any subsequent care occurring in the 1st year. State costs are the annual costs of continued management. All costs are expressed in 1996 U.S. dollars.

RESULTS

As expected, the more severe or debilitating events, such as acute myocardial infarction ($27,630 event cost; $2,185 state cost), generate a greater financial burden than do early-stage complications, such as microalbuminuria ($62 event cost; $14 state cost). Yet, complications that are initially relatively low in cost (e.g., microalbuminuria) can progress to more costly advanced stages (e.g., end-stage renal disease, $53,659 state cost); therefore, minor complications should also be considered in any economic analysis of diabetes.

CONCLUSIONS

The recent literature has lacked cost estimates that may be readily translated into patient-level cost inputs for an economic model. Emerging therapies that may reduce the incidence of some diabetic complications will need to be scrutinized economically in today's cost-conscious environment. The cost estimates from this study provide one piece of the economic analysis needed to evaluate these new interventional therapies.
Usefulness of Revised Fasting Plasma Glucose Criterion and Characteristics of the Insulin Response to an Oral Glucose Load in Newly Diagnosed Japanese Diabetic Subjects
Authors: Tanaka Yasushi , Atsumi Yoshihito , Asahina Takayuki , Hosokawa Kazuhiro , Matsuoka Kenpei , Kinoshita Junichiro , Onuma Tomio , Kawamori Ryuzo
Published: March 2007

OBJECTIVE

To examine the usefulness of the revised criterion for fasting plasma glucose (FPG) in the diagnosis of diabetes recommended by the American Diabetic Association (ADA) (126 mg/dl, 7 mmol/1), and to characterize insulin response during the 75-g oral glucose tolerance test (OGTT) in newly diagnosed Japanese diabetic subjects.

RESEARCH DESIGN AND METHODS

A series of 2,121 Japanese subjects underwent a 75-g OGTT (0–3 h) and were divided into three groups (normal glucose tolerance [NGT], impaired glucose tolerance [IGT], and diabetes mellitus [DM]) according to the current World Health Organization criteria. After the cutoff values of FPG that distinguish NGT and IGT from diabetes were analyzed, the usefulness of the ADA criterion for FPG was examined by comparing diagnostic parameters (sensitivity, specificity, and accuracy) with those for the cutoff value of 140 mg/dl. To assess insulin response, both the insulinogenic index (Islx), a marker of early secretion, and the area under the insulin response curve (AUCIns), a marker of total secretion, were compared between the DM, NGT, and 1GT groups.

RESULTS

First, the FPG cutoff value distinguishing NGT from diabetes was 109 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs. 0.31), the same specificity (1.00), and a higher accuracy (0.82 vs. 0.74) than an FPG of 140 mg/dl, and it had a higher specificity (1.00 vs. 0.86) with a slightly lower accuracy (0.82 vs. 0.85) than an FPG of 109 mg/dl. Second, the FPG cutoff value differentiating IGT from diabetes was 113 mg/dl. An FPG of 126 mg/dl showed a higher sensitivity (0.52 vs. 0.31) and accuracy (0.80 vs. 0.74) and a similar specificity (0.97 vs. 1.00) compared with an FPG of 140 mg/dl, and it had a higher specificity (0.97 vs. 0.82) with the same accuracy (0.80) as an FPG of 113 mg/dl. Third, the DM group showed the lowest Islx among the three groups at all FPG values. The AUCIns in the DM group increased along with FPG, reached the maximum level at an FPG of 110 mg/dl, and declined thereafter. AUCIns was higher in the DM group than in the NGT group at FPG values ≥100 mg/dl.

CONCLUSIONS

The revised ADA criterion for FPG of 126 mg/dl may improve diagnostic sensitivity without loss of specificity in Japanese diabetic subjects when compared with an FPG criterion of 140 mg/dl. Although early insulin secretion was impaired, total insulin secretion did not seem to be reduced in newly diagnosed Japanese diabetic subjects.
Mortality in Adults With and Without Diabetes in a National Cohort of the U.S. Population, 1971–1993
Authors: Gu Ken , Cowie Catherine C , Harris Maureen I
Published: March 2007

OBJECTIVE

To examine 22-year mortality (1971–1993), causes of death, life expectancy, and survival in a national sample of diabetic and nondiabetic adults according to age, sex, and race.

RESEARCH DESIGN AND METHODS

A representative national cohort of 14,374 adults aged 25–74 years was identified in 1971–1975 in the First National Health and Nutrition Examination Survey (NHANES I). Diabetes was ascertained by medical history interview. The cohort was followed for mortality through 1992–1993, with verification of vital status for 96.2% (n = 13,830). Causes of death were determined from death certificates.

RESULTS

Diabetic subjects comprised 5.1% of the cohort and accounted for 10.6% of the deaths. Mortality for diabetic subjects increased from 12.4 per 1,000 person-years for those aged 25–44 years at baseline to 89.7 per 1,000 person-years for those aged 65–74 years. The age-adjusted mortality rate was 57% higher for diabetic men than for diabetic women; the rate was 27% higher for diabetic non-Hispanic blacks than for diabetic non-Hispanic whites. Mortality rates were highest for insulin-treated subjects and for those with ≥15 years' duration of diabetes. Diabetes was listed on the death certificate as the underlying cause of death for only 7.7% of diabetic men and 13.4% of diabetic women. Considering multiple causes of death, heart disease was listed the most frequently and was present on 69.5% of death certificates of people with diabetes. Death rates were higher for diabetic than for nondiabetic subjects in all age, sex, and race groups. The relative risk of death (diabetic versus nondiabetic subjects) declined with age from a value of 3.6 for those aged 25–44 years at baseline to 1.5 for those aged 65–74 years. The relative risk was elevated in diabetic subjects for all major causes of death except malignant neoplasms. Survival of diabetic subjects was lower than that of nondiabetic subjects in all age, sex, and race groups. Median life expectancy was 8 years lower for diabetic adults aged 55–64 years and 4 years lower for those aged 65–74 years.

CONCLUSIONS

In this representative national sample of adults, mortality rates were higher for diabetic men than for diabetic women and for diabetic blacks than for diabetic whites. The study confirms the substantially higher risk of death, lower survival, and lower life expectancy of diabetic adults compared with nondiabetic adults.