bluuebunny/crossref_metadata_2025 huggingface dataset:
Extra-Pancreatic Manifestations in Diabetes Secondary to Mitochondrial DNA Point Mutation Within the tRNALeu(UUR) Gene
Authors: Vialettes Bernard , Paquis-Fluckinger Véronique , Silvestre-Aillaud Pascale , Dahan David Ben , Pelissier Jean-François , Etchary-Bouyx Frédérique , Raccah Denis , Gin Henri , Guillausseau Pierre Jean , Vanuxen Danielle , Orsini Frederic , Pouget Jean , Cozzone Patrick , Desnuelle Claude
Published: March 2007

OBJECTIVE

A point mutation in the mitochondrial genome has been identified as a cause of diabetes and deafness. We report two pedigrees with and A-to-G transition at nucleotide 3243 of mtDNA within the tRNALeu(UUR) gene and focus our investigations on other localizations of the anomaly, particularly muscle and retina.

RESEARCH DESIGN AND METHODS

Muscular localization has been studied in probands by invasive and noninvasive methods, including muscle biopsy (evaluation of the proportion of mutated mtDNA in comparison to blood cells, measurement of respiratory chain complex activities and histological and histochemical aspects) and 31P-nuclear magnetic resonance (NMR) spectroscopy. Ophthalmic and angiographic examination of retina, electroretinography, and visual evoked potentials were performed in five subjects.

RESULTS

This mutation, previously described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), was expressed more abundantly in muscle than in nucleated blood cells. This low expression in blood cells could hamper the diagnosis for some patients. In addition, despite poor clinical expression, muscle was found to be highly affected. Ragged red fibers and dystrophic mitochondria were observed in muscle biopsy. Histochemical assays showed decreased activity of respiratory chain complexes, and 31P-NMR in vivo data further confirmed the defect of muscle oxidative processes. Exercise-induced lactate production was increased. Finally, in both families, an atypical “salt and pepper” pigmentary retinopathy was observed without consequences on visual acuity.

CONCLUSIONS

In diabetes secondary to 3243 mtDNA mutation, infraclinical muscular and ocular lesions are frequent. These two locations of the disease, which are easily investigated by simple methods, can help in the diagnosis of this new type of diabetes.
Physiological Modulation of Plasma Free Fatty Acid Concentrations by Diet: Metabolic implications in nondiabetic subjects
Authors: Wolever Thomas M S , Bentum-Williams Anita , Jenkins David J
Published: March 2007

OBJECTIVE

To determine the effect of varying the amount of carbohydrate and glycemic index (GI) of breakfast test meals on plasma free fatty acid (FFA) responses of nondiabetic subjects and to see whether the glycemic response at lunch was related to the plasma FFA response to breakfast.

RESEARCH DESIGN AND METHODS

We studied eight subjects over a 6-h period on four separate occasions using a randomized Latin-square design. They received isocaloric breakfast test meals that were either high (84 g) or low (41 g) in carbohydrate and had either a high (∼ 100) or a low (∼ 70) GI, followed by a standard lunch 4 h later.

RESULTS

The initial fall in plasma FFAs after breakfast was similar for all four test meals, but the extent of rebound differed significantly. The mean plasma FFA concentration just before the start of lunch (4 h) was highest after the low-GI, low-carbohydrate breakfast (418 ± 42 mumol/l), followed by high-GI, low-carbohydrate (277 ± 48 μmol/l), high-GI, high carbohydrate (227 ± 32 μmol/l), and low-GI, high-carbohydrate (149 ± 23 μmol/l) (P < 0.01). The concentration of plasma FFAs at 4 h was directly related to the total area under the glycemic response curve to lunch (r = 0.691, n = 32, P < 0.0001).

CONCLUSIONS

In nondiabetic subjects, the type and amount of carbohydrate eaten at breakfast influences the plasma glucose, insulin, and FFA responses to breakfast and also affects the glucose, insulin, and FFA responses to a subsequent standard lunch. The glycemic responses after lunch were closely related to the plasma FFA concentration 4 h after breakfast, which we speculate is due to the inhibitory effect of FFAs on insulin action.
High Prevalence of Diabetic Retinopathy and Nephropathy in Polynesians of Western Samoa
Authors: Collins Veronica R , Dowse Gary K , Plehwe Walter E , Imo Tofaeono T , Toelupe Palanitina M , Taylor Hugh R , Zimmet Paul Z
Published: March 2007

OBJECTIVE

To determine the prevalence of diabetic retinopathy and nephropathy retinopathy and nephropathy and to define associated risk factors in Polynesian Western Samoans with non-insulin-dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

A 1991 population-based study in Samoan adults (ages 25–74 years) included a 75-g oral glucose tolerance test, anthropometric measurements, and blood pressure recordings. Subjects with NIDDM or IGT had 45-degree stereo photographs taken (n = 263) (three standard fields of the right eye), and retinopathy was graded in comparison with Airlie House photographs. First-morning urine samples (n = 304) were also collected from these subjects and from a subsample with normal glucose tolerance. Urinary albumin concentration (UAC) was measured by radio-immunoassay: microalbuminuria was defined as UAC of 30–299 μg/ml; and macroalbuminuria was defined as UAC ≥300 μg/ml.

RESULTS

The prevalence of diabetic retinopathy was 43.2% among subjects with known diabetes and 15.4% in those newly diagnosed. Proliferative diabetic retinopathy was found in 4.5% of known diabetic subjects. The prevalence of elevated UAC was 15.0% in subjects with IGT, 26.0% in newly diagnosed diabetes subjects, and 23.4% in known diabetes subjects. For all diabetic subjects (n = 162), the factors independently associated with diabetic retinopathy (logistic regression) were duration of diabetes, fasting plasma glucose, and body mass index (inversely). Duration of diabetes, serum triglyceride concentrations, and systolic blood pressure were independently associated with elevated UAC in all diabetic subjects (n = 138), and fasting plasma glucose had borderline significance.

CONCLUSIONS

Diabetic retinopathy and albuminuria are common in Polynesian Western Samoans. Duration of diabetes and level of glycemia were the most important associated factors. These data underline the need for cost-effective programs for the detection and early treatment of diabetes in Western Samoa and other developing populations with high susceptibility to NIDDM.
1,5-Anhydro-D-glucitol Evaluates Daily Glycemic Excursions in Well-Controlled NIDDM
Authors: Kishimoto Michihiko , Yamasaki Yoshimitsu , Kubota Minoru , Arai Katsumi , Morishima Toyohiko , Kawamori Ryuzo , Kamada Takenobu
Published: March 2007

OBJECTIVE

To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG) as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG, HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from which the M-value (after Schlichtkrull) was calculated as an index of daily glycemic excursion.

RESEARCH DESIGN AND METHODS

The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15).

RESULTS

HbA1c values were similar among all the groups (diet, 6.9 ± 0.6; OHA, 7.2 ± 0.5; CIT, 7.1 ± 0.6; MIT, 7.2 ± 0.5%). The MIT group showed a significantly higher 1,5-AG concentration (11.5 ± 5.3 μg/ml), a significantly lower M-value (9.2 ± 5.2), and little risk of hypoglycemia (< 4 mmol/l) and hyperglycemia (> 10 mmol/l) (1.3 ± 1.1 times/24 h) compared with the CIT group (6.9 ± 3.3μg/ml, 15.7 ± 8.9, 2.2 ± 1.6 times/24 h, respectively). Insulin doses (22.4 ± 4.5 vs. 22.0 ± 8.9 U/day), FPG (6.6 ± 2.2 vs. 7.4 ± 2.4 mmol/l), and HbA1c concentrations were not significantly different between the CIT and MIT groups. M-values significantly correlated with 1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations.

CONCLUSIONS

The findings suggest that the plasma 1,5-AG concentration can be a useful index of the daily excursion of blood glucose, especially in patients with well-controlled NIDDM.
Insulin Therapy for Diabetic Ketoacidosis: Bolus insulin injection versus continuous insulin infusion
Authors: Butkiewicz Eryn K , Leibson Cynthia L , O'Brien Peter C , Palumbo Pasquale J , Rizza Robert A
Published: March 2007

OBJECTIVE

Despite widespread acceptance of continuous insulin infusion (CII) over bolus insulin injection (BII) for treatment of diabetic ketoacidosis (DKA), there are no population-based studies demonstrating whether CII has resulted in lower morbidity and mortality.

RESEARCH DESIGN AND METHODS

We addressed this issue using a provider-linked database and retrospectively reviewing the complete medical records of all incidence cases of diabetes among Rochester, Minnesota, residents from 1950 to 1989 with a discharge diagnosis of DKA. This population-based study describes the consequences of the widespread change in treatment modality outside the confines of a controlled clinical trial.

RESULTS

Among the diabetes incident cohort, there were 59 subjects with confirmed first episodes of DKA during 1950-1992; 29 of 30 subjects treated with BII occurred before 1970. All 29 CII cases occurred between 1976 and 1992. Sex, etiology, diabetes duration, and age at DKA were similar for the two groups. The proportion of obese individuals (BII = 2/28, CII = 8/21; P = 0.01) differed between groups. The CII group exhibited higher glucose values (BII = 24.9 ± 8.5 mmol/l, CII = 37.1 ± 15.1 mmol/l; P = 0.002) and lower bicarbonate values (BII = 7.7 ± 3.0 nmol/l, CII = 6.2 ± 2.9 nmol/l; P = 0.04) upon admission. The mean quantity of insulin administered was higher in the BII group than in the CII group (179 ± 140 and 99 ± 70 U, P < 0.006). The outcome of hypoglycemia occurred more frequently in the BII group than in the CII group (BII = 8/30, CII = 1/29; P = 0.03). The proportion with hypokalemia, neurological deficit, myocardial arrhythmia, or mortality did not differ significantly between groups.

CONCLUSIONS

Our findings suggest the introduction of CII was accompanied by a decreased incidence of hypoglycemia.
Effects of a Behavioral Weight Loss Program Stressing Calorie Restriction Versus Calorie Plus Fat Restriction in Obese Individuals With NIDDM or a Family History of Diabetes
Authors: Pascale Randy W , Wing Rena R , Butler Betsy A , Mullen Monica , Bononi Patricia
Published: March 2007

OBJECTIVE

The aim of this randomized trial was to compare the effects of a behavioral intervention focusing on either calorie restriction alone or calorie plus fat restriction on weight loss and changes in lipids and glycemic control in individuals with non-insulin-dependent diabetes mellitus (NIDDM) or a family history of diabetes.

RESEARCH DESIGN AND METHODS

We recruited 44 obese women with NIDDM and 46 obese women with a family history of NIDDM and randomly assigned these subjects to calorie restriction (CAL) or to calorie plus fat restriction (CAL + FAT). All subjects participated in a 16-week behavioral weight loss program, with training in diet, exercise, and behavior modification. Subjects assigned to the CAL condition were given a 1,000−1,500 kcal/day goal and self-monitored calories consumed. Subjects assigned to the CAL + FAT condition had the same calorie goal, but were also given a fat goal (grams of fat/day), to produce a diet with < 20% of calories from fat; this group monitored both calories and fat grams.

RESULTS

Among NIDDM subjects, weight loss of the subjects in the CAL+FAT condition was significantly > subjects in the CAL condition (7.7 vs. 4.6 kg) and the CAL+FAT condition group also maintained their weight loss better at the 1-year follow-up (5.2 vs. 1.0 kg). Significant decreases in glucose, high-density lipoprotein (HDL) cholesterol, and total cholesterol were seen after 16 weeks of treatment among NIDDM subjects; these changes were similar in CAL and CAL+FAT groups, but a greater proportion of subjects in CAL condition required oral hypoglycemic medication. At the 1-year follow-up, all parameters had returned to baseline. No significant differences in weight loss or physiological changes were seen between CAL and CAL+FAT conditions in subjects with a family history of diabetes.

CONCLUSIONS

These results suggest that using the combination of calorie and fat restriction may help promote weight loss in obese NIDDM patients. No other long-term benefits of this regimen were observed.
Comparative Validity of a Food Frequency Questionnaire for Adults with IDDM
Authors: Riley Malcolm D , Blizzard Leigh
Published: March 2007

OBJECTIVE

To investigate the characteristics of a food frequency questionnaire (FFQ) in measuring dietary intake in an adult insulin-dependent diabetes mellitus (IDDM) population. FFQs have been widely used in developed countries to assess usual dietary intake; however, information regarding the application of the method to individuals advised to follow a specific dietary regimen (such as people with IDDM) is scarce.

RESEARCH DESIGN AND METHODS

The measurement of energy and macronutrients by an interviewer-administered FFQ was assessed in 84 adults, who were representative of adults with IDDM in Tasmania, Australia, by comparing it with 2 days of weighed dietary records. Mean daily energy and macronutrient intakes by each method were compared, and Pearson correlation coefficients were calculated for both unadjusted and energy-adjusted macronutrient intakes.

RESULTS

The ratio of within-person to between-person variance in dietary estimates from weighed records was 0.53 for energy, 0.70 for fat, 2.55 for protein, 0.50 for carbohydrate, 0.78 for saturated fat, and 3.56 for dietary cholesterol. The correlation coefficient between the FFQ and a 2-day weighed dietary record for the same nutrients ranged from 0.38 for protein intake to 0.60 for saturated fat intake. The correlation coefficient between the FFQ and true usual dietary intake was estimated to be 0.60 for energy-adjusted fat intake, 0.36 for energy-adjusted protein intake, 0.72 for energy-adjusted carbohydrate intake, 0.55 for energy-adjusted saturated fat intake, and 0.77 for energy-adjusted cholesterol intake.

CONCLUSIONS

People with IDDM had a low ratio of within-person to between-person variance in daily energy, fat, carbohydrate, saturate fat, and cholesterol intake. The performance of the FFQ in the IDDM population is consistent with similar questionnaires in nondiabetic populations; however, there was a significant decrease in the dietary energy estimate upon readministration of the questionnaire. Validation studies such as this are important to provide information to guide the design and analysis of investigations that use dietary questionnaires.
Prevalence and Determinants of Glucose Intolerance in a Dutch Caucasian Population: The Hoorn Study
Authors: Mooy Johanna M , Grootenhuis Peter A , Vries Hendrik de , Valkenburg Hans A , Bouter Lex M , Kostense Pieter J , Heine Robert J
Published: March 2007

OBJECTIVE

To study the prevalence and determinants of glucose intolerance in a general Caucasian population.

RESEARCH DESIGN AND METHODS

A random sample of 50- to 74-year old Caucasians (n = 2,484) underwent oral glucose tolerance tests. Multiple regression analyses were performed to study the association of 2-h postload plasma glucose values with potential determinants.

RESULTS

Prevalence of known and newly detected diabetes and impaired glucose tolerance was 3.6, 4.8, and 10.3%, respectively. In women, but not in men, the association of body mass index with 2-h glucose was fully accounted for by the waist-to-hip ratio. Maternal history of diabetes was twice as prevalent as paternal history, but paternal history only was associated with 2-h glucose. In addition, paternal history was a stronger determinant in men than in women. An independent positive association with 2-h plasma glucose was found for alcohol use of > 30 g/day in women and for intake of total protein, animal protein, and polyunsaturated fatty acids in men. An independent inverse association with 2-h plasma glucose was demonstrated for height (both sexes), alcohol use of ≤ 30 g/day (both sexes), energy intake (in men), and, unexpectedly, current smoking (in men).

CONCLUSIONS

The prevalence of diabetes in elderly Caucasians was 8.3%. In men, dietary habits may unfavorably influence glucose tolerance independent of obesity.
Simultaneous Acute Cerebral and Pulmonary Edema Complicating Diabetic Ketoacidosis
Authors: Young Martin C
Published: March 2007

OBJECTIVE

To report on a child with diabetic ketoacidosis (DKA) who developed simultaneous acute cerebral edema (CE) and pulmonary edema (PE), required extracorporeal membrane oxygenation (ECMO), and yet survived without significant neurological or pulmonary handicap.

CASE SUMMARY

A 3-year-old girl with DKA as the first manifestation of insulin-dependent diabetes mellitus (IDDM) sustained coincident acute CE and PE 9 h into therapy. The former responded to mannitol, but the latter matured into adult respiratory distress syndrome (ARDS) resistant to conventional management and requiring ECMO.

CONCLUSIONS

CE, PE, and ARDS can complicate DKA. Survival without sequelae is possible with aggressive treatment.
Variation in the Incidence and Proportion of Diabetes-Related Amputations in Minorities
Authors: Lavery Lawrence A , Ashry Hisham R , Van Houtum William , Pugh Jacqualine A , Harkless Lawrence B , Basu Srabashi
Published: March 2007

OBJECTIVE

To identify the age-adjusted and level-specific incidence of amputations associated with diabetes in Hispanics, African-Americans, and non-Hispanic whites.

RESEARCH DESIGN AND METHODS

We used a database from the Office of Statewide Planning and Development in California that identified all hospitalizations for lower-extremity amputations in the state in 1991. Amputation level was defined by ICD-9-CM codes 84.11–84.18 and were categorized as toe, foot, leg, and thigh amputations.

RESULTS

The age-adjusted incidence of diabetes-related amputation per 10,000 persons with diabetes in 1991 was 95.25 in African-Americans, 55.98 in non-Hispanic whites, and 44.43 in Hispanics. Hispanics had a higher proportion of amputations (82.7%) associated with diabetes than did African-Americans (61.6%) or non-Hispanic whites (56.8%) (P < 0.001). African-Americans had the highest age-adjusted incidence rate for each level in people with and without diabetes. African-Americans underwent more proximal amputations compared with non-Hispanic whites and Hispanics (P < 0.001). Diabetes-related amputations were 1.72 and 2.17 times more likely in African-Americans compared with non-Hispanic whites and Hispanics, respectively.

CONCLUSIONS

Hispanics had proportionally more amputations associated with diabetes than did African-Americans or non-Hispanic whites. A significant excess incidence of both diabetes- and non-diabetes-related amputations and proportionally more proximal amputations were identified in African-Americans compared with Hispanics and non-Hispanic whites. A possible explanation could be the higher prevalence of peripheral vascular disease in African-Americans. Public health initiatives, which have been demonstrated to reduce the incidence of diabetes-related lower-extremity amputations, should be implemented, and additional work should focus on minority groups.
Polymorphism of Complement C4 and Susceptibility to IDDM and Microvascular Complications
Authors: Lhotta Karl , Auinger Martin , Kronenberg Florian , Irsigler Karl , König Paul
Published: March 2007

OBJECTIVE

The aim of this study was to investigate whether or not the inherited polymorphism of complement C4 is associated with genetic susceptibility to microvascular complications in IDDM as previously reported.

RESEARCH DESIGN AND METHODS

We determined C4 phenotypes in 241 patients with IDDM and 140 healthy control subjects by agarose gel electrophoresis and immunoprecipitation. C4 allotype frequencies were compared between patients and healthy control subjects. In addition, we compared allotype frequencies of 83 patients with nephropathy with those of 80 patients without nephropathy and compared those of 50 patients with proliferative retinopathy with those of 68 patients without retinopathy or background retinopathy. Duration of IDDM in control patients was at least 21 years.

RESULTS

Patients and healthy control subjects differed at both the C4A (P < 0.00001) and C4B (P < 0.0005) loci. The C4 null allele C4AQ0 was significantly increased in IDDM patients (26.8 vs. 11.8%, P < 0.005). C4B2 was more frequently observed in patients (14.5 vs. 6.8%, P < 0.05) compared with healthy control subjects. No differences were observed in C4 allotype distribution between patients with and without nephropathy or retinopathy.

CONCLUSIONS

These data confirm previous reports of an association between the C4 null allele C4AQ0 and IDDM. Our results do not support an association of the inherited polymorphism of complement C4 with genetic susceptibility to microvascular complications in patients with IDDM.
High-Fat and High-Carbohydrate Diets and Energy Balance
Authors: Shah Meena , Garg Abhimanyu
Published: March 2007

The current American Diabetes Association guidelines for nutrition recommend a moderate increase in monounsaturated fats and a reduced intake of carbohydrate in patients with diabetes in whom high-carbohydrate diets deteriorate glycemic control and lipoprotein levels. High-fat diets, however, are believed to promote obesity, and some investigators may have reservations recommending such diets. This review thus investigates the role of diet composition in promoting obesity or achieving weight loss and its implications in patients with diabetes. Epidemiological studies show some evidence that fat intake is more importantly related to body weight than carbohydrate intake, but conclusions are weak because confounding variables, such as physical activity, smoking, and energy intake, were generally not controlled for. Metabolic studies under isoenergic conditions report no change in energy balance when fat intake is increased, but report a negative fat balance with substantial increase carbohydrate intake. During overfeeding, excess fat intake is stored as fat, whereas excess carbohydrate is mostly oxidized in the short term but can lead to substantial gain in fat stores because of reduced fat oxidation and considerable de novo lipogenesis in the long term. Spontaneous energy intake, however, is higher on an unrestricted high-fat diet compared with a high-carbohydrate diet, but the long-term effects are not known. Weight-loss intervention studies show that a hypocaloric high-carbohydrate diet is not associated with more weight loss than a high-fat hypocaloric diet. In conclusion, a high-monounsaturated fat diet to control glycemic control and lipoprotein levels in patients with diabetes should not affect weight loss or maintenance, provided that energy intake is carefully controlled.
Glimepiride, a New Once-Daily Sulfonylurea: A double-blind placebo-controlled study of NIDDM patients
Authors: Rosenstock Julio , Samols Ellis , Muchmore Douglas B , Schneider Jill ,   The Glimepiride Study Group
Published: March 2007

OBJECTIVE

To compare the efficacy and safety of two daily doses of the new sulfonylurea, glimepiride (Amaryl), each as a once-daily dose or in two divided doses, in patients with NIDDM.

RESEARCH DESIGN AND METHODS

Of the previously treated NIDDM patients, 416 entered this multicenter randomized double-blind placebo-controlled fixed-dose study. After a 3-week placebo washout, patients received a 14-week course of placebo or glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i.d.

RESULTS

Fasting plasma glucose (FPG) and HbA1c values were similar at baseline in all treatment groups. The placebo group's FPG value increased from 13.0 mmol/l at baseline to 14.5 mmol/l at the last evaluation endpoint (P ≤ 0.001). In contrast, FPG values in the four glimepiride groups decreased from a range of 12.4–12.9 mmol/l at baseline to a range of 8.6–9.8 mmol/l at endpoint (P ≤ 0.001, within-group change from baseline; P ≤ 0.001, between-group change [vs. placebo] from baseline). Two-hour postprandial plasma glucose (PPG) findings were consistent with FPG findings. In the placebo group, the HbA1c value increased from 7.7% at baseline to 9.7% at endpoint (P ≤ 0.001), whereas HbA1c values for the glimepiride groups were 7.9–8.1% at baseline and 7.4–7.6% at endpoint (P ≤ 0.001, within-group change from baseline; P ≤ 0.001, between-group change from baseline). There were no meaningful differences in glycemic variables between daily doses of 8 and 16 mg or between once- and twice-daily dosing. Adverse events and laboratory data demonstrate that glimepiride has a favorable safety profile.

CONCLUSIONS

Glimepiride is an effective and well-tolerated oral glucose-lowering agent. The results of this study demonstrate maximum effectiveness can be achieved with 8 mg q.d. of glimepiride in NIDDM subjects.
Treatment of Osteomyelitis in the Diabetic Foot: Contribution of conservative surgery
Authors: Ha Van Georges , Siney Hubert , Danan Jean-Paul , Sachon Claude , Grimaldi André
Published: March 2007

OBJECTIVE

To compare the duration of healing of foot ulcers with osteomyelitis in diabetic patients treated by medical treatment versus medical treatment associated with conservative orthopedic surgery.

RESEARCH DESIGN AND METHODS

We entered into the study 67 diabetic patients who had a foot ulcer with osteomyelitis without ischemia requiring a peripheral arterial reconstruction. Thirty-two diabetic patients were included in a first historic group from 1986 to 1993, treated by antibiotic therapy, offloading, and wound care. Thirty-two patients were included from September 1993 to March 1995, treated by the same medical treatment and conservative orthopedic surgery.

RESULTS

The healing rate was 57% in the group treated by the medical treatment alone versus 78% in the surgical group (P < 0.008). The duration of healing was 462 ± 98 days versus 181 ± 30 days (P < 0.008).

CONCLUSIONS

Conservative surgery contributes to an increase in the healing rate of foot ulcers with osteomyelitis compared with a medical treatment alone.
Abnormal Glucose Tolerance and Other Coronary Heart Disease Risk Factors in an Isolated Aboriginal Community in Central Australia
Authors: Gault Andrew , O'Dea Kerin , Rowley Kevin G , McLeay Toby , Traianedes Kathy
Published: March 2007

OBJECTIVE

To determine the age- and sex-specific prevalence of diabetes, impaired glucose tolerance (IGT), and coronary heart disease risk factors in a remote central Australian Aboriginal community maintaining some degree of traditional lifestyle, living in homeland communities on their ancestral land.

RESEARCH DESIGN AND METHODS

A cross-sectional survey of 437 subjects ≥ 15 years of age (189 men, 248 women), representing 80% of the adult population residing in the community at the time of the survey, was performed and the following parameters measured: BMI, glucose tolerance, circulating insulin and lipids, and blood pressure.

RESULTS

The mean BMI for this population was 22.9 ± 4.8 kg/m2. The prevalence of diabetes in the age group of 15–34 years (103 men and 140 women) was 2 and 6% for men and women, respectively. In the 35-years-and-older age group (86 men and 108 women), diabetes prevalence was 19 and 13% for men and women, respectively. Over half the diabetic subjects did not exhibit fasting hyperglycemia. IGT occurred in 8 and 15% of younger men and women, respectively, and in 17 and 32% of older men and women, respectively. Smoking was common among men (53% current smokers) but rare among women (2% current smokers). The prevalence of hypercholesterolemia, hypertriglyceridemia, hypertension, and overweight rose with increasing degrees of glucose intolerance. The two communities adjacent to the only store in the area had a higher prevalence of abnormal glucose tolerance than did the more remote homeland communities (odds ratio for abnormal glucose tolerance: 2.92; 95% CI 1.51−5.63).

CONCLUSIONS

Despite their relative leanness, this Aboriginal population exhibited relatively high prevalences of IGT and diabetes without fasting hyperglycemia. The data suggest a protective effect of a decentralized mode of living, as opposed to a more urbanized lifestyle, on the occurrence of glucose intolerance. Abnormal lipid profiles (particularly high triglycerides and low HDL cholesterol) and the high prevalence of smoking in men indicated a high-risk profile for coronary heart disease in this population.
Lipoatrophy With Human Insulin
Authors: Jaap Alan J , Horn Helen M , Tidman Michael J , Walker James D
Published: March 2007

We describe a case of lipoatrophy that was secondary to human insulin. The patient had only ever been treated with human insulin, and the lipoatrophy appeared to partially resolve with continued use of the same insulin preparations. Possible underlying pathogenic mechanisms are discussed.
NIDDM in the elderly
Authors: Meneilly Graydon S , Elliott Thomas , Tessier Daniel , Hards Lori , Tildesley Hugh
Published: March 2007

OBJECTIVE

We conducted this study to assess the metabolic alterations in elderly patients with NIDDM.

RESEARCH DESIGN AND METHODS

Healthy, lean (n = 15; age, 73 ± 1 years; BMI, 23.8 ± 0.5 kg/m2), and obese (n = 10; age, 71 ± 1 years; BMI, 28.9 ± 1.2 kg/m2) control subjects and lean (n = 10; age, 75 ± 2 years; BMI, 24.0 ± 0.5 kg/m2) and obese (n = 23; age, 73 ± 1 years; BMI, 29.9 ± 0.7 kg/m2) NIDDM patients underwent a 3-h glucose tolerance test, a 2-h hyperglycemic glucose clamp study, and a 3-h euglycemic glucose clamp study with tritiated glucose methodology to measure glucose production and disposal rates.

RESULTS

Waist-to-hip ratio (WHR) was greater in both lean and obese NIDDM patients than in control subjects. Insulin responses during the oral glucose tolerance test were similar in obese subjects (control subjects: 417 ± 64 pmol/l; NIDDM patients: 392 ± 47 pmol/l) but were reduced in lean NIDDM patients (control subjects: 374 ± 34 pmol/l; NIDDM patients: 217 ± 20 pmol/l, P < 0.01). Lean and obese NIDDM patients had absent first-phase insulin responses during the hyperglycemic clamp. Second-phase insulin responses were reduced in lean (P < 0.01 vs. control subjects by analysis of variance) but not obese NIDDM patients. Hepatic glucose output was not increased in lean or obese NIDDM patients. Steady-state (150–180 min) glucose disposal rates were 16% less in lean NIDDM patients (control subjects: 8.93 ± 0.37 mg.kg LBM (lean body mass)−1 · min−1; NIDDM patients: 7.50 ± 0.28 mg · kg LBM−1 · min−1, P < 0.05) and 37% less in obese NIDDM patients (control subjects: 8.17 ± 0.38 mg · kg LBM−1 · min−1; NIDDM patients: 5.03 ± 0.36 mg · kg LBM−1 · min−1, P < 0.001).

CONCLUSIONS

Lean elderly NIDDM patients have a profound impairment in glucose-induced insulin release but mild resistance to insulin-mediated glucose disposal. Obese elderly NIDDM patients have adequate circulating insulin, but marked resistance to insulin-mediated glucose disposal. Hepatic glucose output is not increased in elderly NIDDM patients.
Comparison of Different Insulin Regimens in Elderly Patients With NIDDM
Authors: Wolffenbuttel Bruce H R , Sels Jean-Pierre J E , Rondas-Colbers Gabrielle J W M , Menheere Paul P C A , Kruseman Arie C Nieuwenhuijzen
Published: March 2007

OBJECTIVE

To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents.

RESEARCH DESIGN AND METHODS

We studied 95 elderly patients with NIDDM (age 68 ± 9 years, BMI 26.0 ± 4.6 kg/m2, and median time since diagnosis of diabetes 9 years [range 1–37]; 37 men, 58 women), who were poorly controlled, despite diet and maximal doses of oral antihyperglycemic agents. Three insulin administration regimens were compared during a 6-month period: patients were randomized for treatment with a two-injection scheme (regimen A) or a combination of glibenclamide with one injection of NPH insulin, administered either at bedtime (regimen B) or before breakfast (regimen C), and insulin treatment was mainly instituted in an outpatient setting.

RESULTS

After 6 months of insulin treatment, fasting blood glucose of the total patient population had decreased from an average of 14.1 ± 2.2 to 8.3 ± 2.0 mmol/l (P < 0.001), and HbA1c fell from 11.0 ± 1.3 to 8.3 ± 1.2% (P < 0.001); 34 patients reached HbA1c levels below 8.0%, 25 of them even below 7.5%. With two insulin injections daily, HbA1c decreased from 11.2 ± 1.3 to 8.2 ± 1.2%, while during combined treatment, HbA1c fell from 10.5 ± 1.2 to 8.1 ± 1.1% (regimen B) and from 11.1 ± 1.3 to 8.5 ± 1.1% (regimen C). Comparable improvement of the other measures of glycemic control, lipids and lipoproteins, was observed in the different treatment regimens. Body weight increase was moderate (mean ± 4.0 kg) and similar in all patient groups. One-third of patients starting with one insulin injection daily needed a second injection to control glycemia. One episode of severe hypoglycemia was observed. Combined insulin-sulfonylurea treatment was almost 20% more expensive than twice-daily administration of insulin alone.

CONCLUSIONS

Insulin treatment can safely be instituted in elderly patients with NIDDM. However, it is difficult to obtain optimal glycemic control. Insulin has moderate beneficial effects on serum lipoproteins. Although on the basis of glycemic control and weight gain, no preference for any treatment regimen can be discerned, twice-daily insulin administration is the most simple and cost-effective regimen.
Does Hyperinsulinemia Preserve Bone?
Authors: Barrett-Connor Elizabeth , Kritz-Silverstein Donna
Published: March 2007

OBJECTIVE

Obesity and NIDDM are each associated with increased bone mineral density (BMD). We therefore hypothesize that hyperinsulinemia is an osteogenic factor.

RESEARCH DESIGN AND METHODS

Subjects consisted of 411 men and 559 women aged 50–89 years who were participants in the Rancho Bernardo Heart and Chronic Disease Study and were not diabetic by history or oral glucose tolerance test. Fasting and 2-h postchallenge insulin were measured by radioimmunoassay. Bone mineral density was measured at the midshaft radius with single photon absorptiometry and at the lumbar spine and hip with dual energy X-ray absorptiometry.

RESULTS

Multiple regression analyses indicated that among men, a significant insulin-BMD association at the hip was no longer apparent after adjusting for covariates. Among women, fasting insulin was significantly and positively associated with bone density of the radius and spine (P < 0.05), independent of age, BMI, waist-hip ratio, postmenopausal estrogen use, age at menopause, thiazide use, family history of diabetes, current cigarette smoking, and exercise. Each 10 μU/ml increase in fasting insulin was associated with an increase of 0.33 and 0.57 g/cm2 of the radius and spine, respectively.

CONCLUSIONS

Hyperinsulinemia may be responsible for part of the observed association of both diabetes and obesity with BMD in women.
Androgen Activity as a Risk Factor for Impaired Glucose Tolerance in Postmenopausal Women
Authors: Larsson Hillevi , Ahrén Bo
Published: March 2007

OBJECTIVE

Low sex hormone–binding globulin (SHBG) has been proposed as a risk factor for NIDDM development in women. Our aim was to study the relationship between SHBG and androgen activity and glucose tolerance, as well as insulin sensitivity, in women with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

We studied 22 women with IGT and 46 women with normal glucose tolerance (NGT) aged 57–59 years. Free testosterone (androgen activity) was determined as the testosterone-to-SHBG ratio. A World Health Organization 75-g oral glucose tolerance test (OGTT) was performed, and insulin sensitivity was measured with a euglycemic-hyperinsulinemic clamp.

RESULTS

Fasting glucose (P = 0.021), 2-h blood glucose after the OGTT (P < 0.001), and fasting insulin (P = 0.009) were higher in the IGT group, while insulin sensitivity did not differ significantly between the two groups (P = 0.065). We found that SHBG levels were lower in the IGT group (P = 0.004), while the testosterone-to-SHBG ratio was higher in the IGT than in the NGT group (P = 0.004). Insulin sensitivity correlated negatively with testosterone-to-SHBG ratio in both groups. The correlation was higher in the IGT (r = −0.67, P = 0.001) than in the NGT group (r = −0.29, P = 0.047). In contrast, the 2-h blood glucose correlated with testosterone-to-SHBG ratio in the IGT (r = 0.66, P = 0.001) but not the NGT group (r = −0.04, NS).

CONCLUSIONS

Postmenopausal women with IGT have higher androgen activity than women with NGT, and the androgen activity correlates with the degree of glucose intolerance in IGT. Furthermore, in women with IGT, who have a high risk of NIDDM development, androgen activity seems to have an enhanced negative influence on insulin sensitivity. Therefore, androgen activity appears to be a risk factor for IGT.
Is ACE Gene Polymorphism a Useful Marker for Diabetic Albuminuria in Japanese NIDDM Patients?
Authors: Nakajima Shinichi , Baba Tsuneharu , Yajima Yoshitada
Published: March 2007

OBJECTIVE

We studied the relationship between an insertion/deletion (I/D) polymorphism in the ACE gene and albuminuria/proteinuria in Japanese NIDDM patients.

RESEARCH DESIGN AND METHODS

A total of 142 Japanese NIDDM patients (89 men, 53 women) with a known diabetes duration of 14 ± 5 (mean ± SD) years and an age of 56 ± 6 years were divided into three groups according to the stage of nephropathy: 41 patients with normoalbuminuria, 47 patients with microalbuminuria, and 54 with overt proteinuria. The three groups were similar in age, diabetes duration, and recent HbA1c level.

RESULTS

The distribution of DD, ID, and II genotypes of the ACE gene did not differ among the three groups (10, 46, and 44% in the normoalbuminuric patients; 13, 53, and 34% in the microalbuminuric patients; and 15, 46, and 39% in the proteinuric patients, respectively). Meanwhile, the frequency of the D allele in the proteinuric male patients was slightly higher than in the normoalbuminuric male patients (45 vs. 27%, X 2 = 3.9, P < 0.05), while the D allele frequency was nonsignificantly lower in the proteinuric female patients than in the normoalbuminuric female patients.

CONCLUSION

These results did not support the hypothesis that the genotype of the ACE gene would be a clinically useful genetic marker for predicting the development of nephropathy in Japanese NIDDM patients. However, the role of D allele of ACE gene in the progression of nephropathy in male patients remains to be seen.
Injection Site Effects on the Pharmacokinetics and Glucodynamics of Insulin Lispro and Regular Insulin
Authors: Braak Edith W Ter , Woodworth James R , Bianchi Rutgert , Cerimele Benito , Erkelens D Willem , Thijssen Jos H H , Kurtz Darcie
Published: March 2007

OBJECTIVE

The pharmacokinetics and glucodynamics of a new insulin analog, insulin lispro, and regular human insulin were compared and contrasted after subcutaneous administrations in femoral, deltoid, and abdominal injection sites.

RESEARCH DESIGN AND METHODS

Single 0.2 U/kg doses of insulin lispro and regular insulin were administered to 12 healthy subjects in a six-way randomized crossover fashion. Each dose was given after an overnight fast in one of three injection sites: abdominal, deltoid, or femoral. Study drugs were given during a manual euglycemic glucose clamp. Blood samples were collected over the 12-h clamp for measurement of insulin-reactive components, with pharmacokinetic and glucodynamic measurements derived from these serum insulin and clamp measurements.

RESULTS

Glucodynamic comparisons between insulin lispro and regular insulin showed a greater maximum infusion rate (Rmax) at an earlier time (TRmax), regardless of injection site. The total glucose infused (Gtot) showed nearly identical values between sites for insulin lispro. Regular insulin showed greater Gtot values from deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater Gtot, primarily driven by the increased Gtot from deltoid and femoral injections. Greater maximum serum insulin concentrations (Cmax) were experienced with insulin lispro at earlier times (tmax), regardless of the injection site (P < 0.001). Abdominal administrations produced the greatest Cmax values at the earliest tmax for both regular insulin and insulin lispro. Deltoid and femoral injections had lower Cmax values for both compounds. Shifts also occurred with tmax, although these shifts were much greater with regular insulin than with insulin lispro. Equivalent area under the curve (AUC) values were found when compared between compounds.

CONCLUSIONS

Slower absorption from deltoid and femoral administrations resulted in an increased duration of action for both regular insulin and insulin lispro when compared to abdominal administration. However, notable increases in the onset of action were only apparent with regular insulin. The consistency with insulin lispro response from abdominal and extremity injection sites allows more potential sites for subcutaneous injection with an assured rapid response.
Five-Year Prospective Study of Glomerular Filtration Rate and Albumin Excretion Rate in Normofiltering and Hyperfiltering Normoalbuminuric NIDDM Patients
Authors: Silveiro Sandra Pinho , Friedman Rogerio , De Azevedo Mirela Jobim , Canani Luis Henrique , Gross Jorge Luiz
Published: March 2007

OBJECTIVE

To evaluate the evolution of glomerular filtration rate (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients.

RESEARCH DESIGN AND METHODS

A longitudinal study of 32 normoalbuminuric (AER < 20 μg/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml · min−1 x 1.73 m−2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months.

RESULTS

There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline was significantly greater in HF patients (−0.61 ml · min−1.month−1; P = 0.001) than in NF (−0, 18) and control subjects (−0, 14); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 μg/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria.

CONCLUSIONS

The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).
Psychiatric Disorder and Metabolic Control Among Youths With IDDM: A longitudinal study
Authors: Kovacs Maria , Mukerji Protap , Iyengar Satish , Drash Allan
Published: March 2007

OBJECTIVE

To investigate the longitudinal relationship between psychiatric diagnostic variables and metabolic control among youths with IDDM.

RESEARCH DESIGN AND METHODS

A group of 88 youths, 8 to 13 years old at onset of 1DDM, were evaluated repeatedly during a 9-year follow-up period, on average, using a standardized psychiatric protocol. Levels of HbA1 were also assessed repeatedly. Psychiatric diagnoses were derived independently of HbA1 values.

RESULTS

In univariate longitudinal analyses, the psychiatric diagnosis of noncompliance with medical treatment was significantly related to HbA1 level. There was a trend of an association between any major psychiatric disorder, as well as nondepressive disorder, and HbA1 Interaction terms between IDDM duration (or age) and psychiatric variables were also significantly related to metabolic control. According to the final multivariate model of repeatedly assessed HbA1, noncompliance with medical treatment (irrespective of IDDM duration) and the interaction between nondepressive psychiatric disorder and IDDM duration contributed to worse metabolic control.

CONCLUSIONS

We found some support for the hypothesis that psychiatric morbidity negatively affects blood glucose regulation and that its consequences are more marked the longer young patients have had IDDM. We did not confirm the hypothesis that depressive illness has particularly deleterious consequences on metabolic control. Noncompliance with medical treatment and having had nondepressive psychiatric illness in interaction with IDDM duration account for a statistically significant but clinically modest amount of variability in HbA1 over time. The weak relationship among these variables may explain the inconsistent findings in the literature regarding psychiatric morbidity and metabolic control.
Routine Perioperative Dipyridamole 2O1TI Imaging in Diabetic Patients Undergoing Vascular Surgery: Is it necessary?
Authors: Zarich Stuart W , Cohen Mylan C , Lane Stephen E , Mittleman Murray A , Nesto Richard W , Hill Thomas , Campbell David , Lewis Stanley M
Published: March 2007

OBJECTIVE

To assess the utility of dipyridamole thallium testing in symptomatic and asymptomatic patients with diabetes undergoing vascular surgery.

RESEARCH DESIGN AND METHODS

Dipyridamole 201Tl myocardial scmtigraphy was performed preoperatively in 93 consecutive patients with diabetes undergoing peripheral vascular procedures. The utility of clinical and thallium variables in predicting cardiovascular complications was assessed.

RESULTS

Two groups of patients were identified: group A (36 patients) without clinical evidence of cardiac disease and group B (57 patients) with clinical evidence of cardiac disease. Dipyridamole thallium scans were abnormal in 21 of 36 (58%) of group A patients compared with 53 of 57 (93%) of group B patients (P < 0.0001). Compared with group B patients with perfusion defects, group A patients with perfusion abnormalities tended to have fewer defects per scan (2.7 ± 1.5 vs. 3.6 ± 1.9, P = 0.05). No perioperative cardiac complications occurred in group A patients while perioperative cardiac complications occurred in 9 of 57 (16%, 95% CI 7-28%) group B patients (P = 0.01). For the entire study population, the complication rate was 10%.

CONCLUSIONS

Diabetic individuals without clinical markers for coronary artery disease appear to be at low risk for adverse postoperative cardiac events after vascular surgery. Preoperative myocardial perfusion imaging may add little to cardiovascular risk assessment in this subgroup of patients with diabetes.