bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry.
Authors: Berger B , Stenström G , Sundkvist G
Published: March 2007

OBJECTIVE: Our objective was to analyze the prevalence, incidence, and mortality of diabetes in a population of 280,539 inhabitants. RESEARCH DESIGN AND METHODS: The incidence, prevalence, and deaths from diabetes at all ages of a population have been prospectively followed in the county of Skaraborg, Sweden, since 1991. RESULTS: The annual incidence of diabetes per 100,000 inhabitants in 1991-1995 was (mean +/- 95% CI) 14.7 +/- 3.2 for type 1 diabetes (diagnosed at 24.1 +/- 2.2 years of age) and 265.6 +/- 16.1 for type 2 diabetes (diagnosed at 66.6 +/- 0.6 years of age). The incidence of type 2 diabetes was significantly (P < 0.001) higher among men. There was no significant change in the age at diagnosis of diabetes. Although the incidence rate and the age at diagnosis were constant, the prevalence of diabetes increased by 6% each year. The relative mortality risk for diabetic patients was almost four times higher than expected. The median age at death, however, increased significantly, from 77.2 to 80.2 years (P < 0.05), during the study. CONCLUSIONS: The prevalence but not the incidence rate of diabetes increased during the years 1991-1995. Although diabetic patients showed a high relative mortality, increased survival apparently explains the increase in prevalence of diabetes in the country of Skaraborg.
Effect of energy restriction, weight loss, and diet composition on plasma lipids and glucose in patients with type 2 diabetes.
Authors: Heilbronn L K , Noakes M , Clifton P M
Published: March 2007

OBJECTIVE: To determine the optimal diet for improving glucose and lipid profiles in obese patients with type 2 diabetes during moderate energy restriction. RESEARCH DESIGN AND METHODS: A total of 35 free-living obese patients with type 2 diabetes were assigned to one of three 1,600 kcal/day diets for 12 weeks. The diets were high carbohydrate (10% fat, 4% saturated), high monounsaturated fat (MUFA) (32% fat, 7% saturated), or high saturated fat (SFA) (32% fat, 17% saturated). RESULTS: Diet composition did not affect the magnitude of weight loss, with subjects losing an average of 6.6 +/- 0.9 kg. Energy restriction and weight loss resulted in reductions in fasting plasma glucose (-14%), insulin (-27%), GHb (-14%), and systolic (-7%) and diastolic blood pressure (-10%) levels and the glucose response area (-17%) independent of diet composition. Diet composition did affect the lipoprotein profile. LDL was 10% and 17% lower with the high-carbohydrate and high-MUFA diets, respectively, whereas no change was observed with the high-SFA diet (P < 0.001 for effect of diet). HDL was transiently reduced on the high-carbohydrate diet at weeks 1, 4, and 8, whereas higher fat consumption maintained these levels. The total cholesterol:HDL ratio, although significantly reduced on the high-MUFA diet (P < 0.01), was not different from the other two diets after adjustment for baseline differences. CONCLUSIONS: Energy restriction, independent of diet composition, improves glycemic control; however, reducing SFA intake by replacing SFA with carbohydrate or MUFA reduces LDL maximally during weight loss and to a greater degree than has been shown in weight-stable studies.
Effect of troglitazone on body fat distribution in type 2 diabetic patients.
Authors: Mori Y , Murakawa Y , Okada K , Horikoshi H , Yokoyama J , Tajima N , Ikeda Y
Published: March 2007

OBJECTIVE: Troglitazone was recently reported to specifically promote the differentiation of pre-adipocytes into adipocytes in vitro in subcutaneous fat only, indicating a relation to insulin-resistance-improving action of troglitazone. To expand on this finding, we investigated at the clinical level how long-term administration of troglitazone influences the body fat distribution in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Troglitazone (400 mg/day) was administered for 6 months to 30 type 2 diabetic patients whose glycemic control was poor. A total of 18 patients received diet therapy alone (in the single-treatment group, BMI 26.0 +/- 4.6, HbA1c 8.2 +/- 1.7%), and 12 patients concomitantly received glibenclamide (1.25-7.5 mg/day) (in the concomitant sulfonylurea group, BMI 25.4 +/- 4.7, HbA1c 9.2 +/- 1.2%). BMI, HbA1c, serum lipid level, and body fat distribution, which were determined by computed tomography (CT) scan at the umbilical level, were measured and compared before and after troglitazone treatment. RESULTS: During the 6-month troglitazone treatment, HbA1c levels decreased and BMI increased in both groups. As for body fat distribution in the single-treatment group, visceral fat area (VFA) decreased (from 118.3 +/- 54.3 to 101.1 +/- 50.8 cm2; P < 0.001), and subcutaneous fat area (SFA) increased (from 189.7 +/- 93.3 to 221.6 +/- 101.6 cm2; P < 0.001), resulting in a decrease in visceral/subcutaneous (V/S) ratio (from 0.74 +/- 0.48 to 0.50 +/- 0.32; P < 0.001). In the concomitant sulfonylurea group, VFA was unchanged (from 108.1 +/- 53.5 to 112.5 +/- 59.9 cm2), while SFA increased (from 144.6 +/- 122.0 to 180.5 +/- 143.5 cm2; P < 0.01), thereby decreasing the V/S ratio (from 0.91 +/- 0.46 to 0.77 +/- 0.44; P < 0.01). The serum triglyceride level and the area under glucose curve during the 75-g oral glucose tolerance test decreased significantly in the single-treatment group. CONCLUSIONS: According to our data, troglitazone appears to promote fat accumulation in the subcutaneous adipose tissue rather than in the visceral adipose tissue in mildly obese Japanese people with type 2 diabetes. This shift of energy accumulation from the visceral to subcutaneous adipose tissue may greatly contribute to the troglitazone-mediated amelioration of insulin resistance.
Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial.
Authors: Vuksan V , Jenkins D J , Spadafora P , Sievenpiper J L , Owen R , Vidgen E , Brighenti F , Josse R , Leiter L A , Bruce-Thompson C
Published: March 2007

OBJECTIVE: To examine whether Konjac-mannan (KJM) fiber improves metabolic control as measured by glycemia, lipidemia, and blood pressure in high-risk type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 11 hyperlipidemic and hypertensive type 2 diabetic patients treated conventionally by a low-fat diet and drug therapy participated. After an 8-week baseline, all were randomly assigned to take either KJM fiber-enriched test biscuits (0.7 g/412 kJ [100 kcal] of glucomannan) or matched placebo wheat bran fiber biscuits during two 3-week treatment phases separated by a 2-week washout period. The diet in either case was metabolically controlled and conformed to National Cholesterol Education Program Step 2 guidelines, while medications were maintained constant. Efficacy measures included serum fructosamine, lipid profiles, apolipoproteins, blood pressure, body weight, and nutritional analysis. RESULTS: Compared with placebo, KJM significantly reduced the metabolic control primary end points: serum fructosamine (5.7%, P = 0.007, adjusted alpha = 0.0167), total:HDL cholesterol ratio (10%, P = 0.03, adjusted alpha = 0.05), and systolic blood pressure (sBP) (6.9%, P = 0.02, adjusted alpha = 0.025). Secondary end points, including body weight, total, LDL, and HDL cholesterol, triglycerides, apolipoproteins A-1, B, and their ratio, glucose, insulin, and diastolic blood pressure, were not significant after adjustment by the Bonferroni-Hochberg procedure. CONCLUSIONS: KJM fiber added to conventional treatment may ameliorate glycemic control, blood lipid profile, and sBP in high-risk diabetic individuals, possibly improving the effectiveness of conventional treatment in type 2 diabetes.
Excess maternal transmission of type 2 diabetes. The Northern California Kaiser Permanente Diabetes Registry.
Authors: Karter A J , Rowell S E , Ackerson L M , Mitchell B D , Ferrara A , Selby J V , Newman B
Published: March 2007

OBJECTIVE: To assess excess maternal transmission of type 2 diabetes in a multiethnic cohort. Previous studies have reported higher prevalence of diabetes among mothers of probands with type 2 diabetes than among fathers. This analysis is vulnerable to biases, and this pattern has not been observed in all populations or races. RESEARCH DESIGN AND METHODS: We assessed evidence for excess maternal transmission among 42,533 survey respondents with type 2 diabetes (probands) by calculating the prevalence of diabetes in their siblings and offspring. To assess data quality, we evaluated completeness of family history data provided. Accuracy of family information reported by probands was also evaluated by comparing survey responses in a subsample of 206 probands with family histories modified after further interviews with relatives. RESULTS: Siblings (n = 60,532) of probands with affected mothers had a greater prevalence of diabetes (20%) than those with affected fathers (17%) (P < 0.001 for adjusted odds ratios). Prevalence of diabetes was higher among the offspring (n = 72,087) of female (3.4%) versus male (2.2%) probands (P < 0.001 for adjusted odds ratios). These patterns were evident in all races and both sexes; however, the effect size was clinically insignificant in African-Americans and male offspring. In general, probands provided more complete data about diabetes status for the maternal arm of the pedigree than the paternal arm. Completeness of knowledge was not related to proband sex, but was related to education and race, and inversely to age. Accuracy of proband-reported family history was consistently good (kappa statistics generally > 0.70). CONCLUSIONS: Excess maternal transmission was observed in all races and both sexes, although the size of the excess was negligible in African-Americans and male offspring. Potential reporting and censoring biases are discussed.
The 14-year incidence of lower-extremity amputations in a diabetic population. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.
Authors: Moss S E , Klein R , Klein B E
Published: March 2007

OBJECTIVE: To estimate the cumulative 14-year incidence of lower-extremity amputations (LEAs) and evaluate risk factors for LEA. RESEARCH DESIGN AND METHODS: Study subjects consisted of population-based cohorts of younger-onset (diagnosed before age 30 years and taking insulin, n = 906) and older-onset (diagnosed after age 30 years, n = 984) individuals with diabetes. Subjects participated in baseline (1980-1982), 4-year, 10-year, and 14-year examinations or interviews. LEAs were determined by history. RESULTS: The cumulative 14-year incidence of LEA was 7.2% in younger- and 9.9% in older-onset patients. In multivariable analyses based on the discrete linear logistic model, LEA in the younger-onset group was more likely for males (odds ratio [OR] 5.21 [95% CI 2.50-10.88]), older age (OR for 10 years 1.71 [1.30-2.24]), higher glycosylated hemoglobin (OR for 1% 1.39 [1.22-1.59]), higher diastolic blood pressure (OR for 10 mmHg 1.58 [1.20-2.07]), history of ulcers of the feet (3.19 [1.71-5.95]), and more severe retinopathy (OR for one step 1.16 [1.08-1.24]). In younger-onset patients aged > or = 18, pack-years smoked (OR for 10 years 1.20 [1.03-1.41]) was also associated with LEAs, and daily aspirin use was inversely associated (OR 0.11 [0.01-0.83]). In the older-onset group, LEA was more likely for men (2.66 [1.49, 4.76]) and if the subject had higher glycosylated hemoglobin (OR for 1% 1.25 [1.09-1.43]), higher pulse pressure (OR for 10 mmHg 1.19 [1.04-1.37]), history of ulcers (3.56 [1.84-6.89]), and more severe retinopathy (OR for one step 1.07 [1.00-1.13]). CONCLUSIONS: There are several risk factors for LEA with potential for modification and preventive strategies.
A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44)
Authors: Holman R R , Cull C A , Turner R C
Published: March 2007

OBJECTIVE: To determine the degree to which alpha-glucosidase inhibitors, with their unique mode of action primarily reducing postprandial hyperglycemia, offer an additional therapeutic approach in the long-term treatment of type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 1,946 patients (63% men) who were previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The patients were randomized to acarbose (n = 973), titrating to a maximum dose of 100 mg three times per day, or to matching placebo (n = 973). Mean +/- SD age was 59 +/- 9 years, body weight 84 +/- 17 kg, diabetes duration 7.6 +/- 2.9 years, median (interquartile range) HbA1c 7.9% (6.7-9.5), and fasting plasma glucose (FPG) 8.7 mmol/l (6.8-11.1). Fourteen percent of patients were treated with diet alone, 52% with monotherapy, and 34% with combined therapy. Patients were monitored in UKPDS clinics every 4 months for 3 years. The main outcome measures were HbA1c, FPG, body weight, compliance with study medication, incidence of side effects, and frequency of major clinical events. RESULTS: At 3 years, a lower proportion of patients were taking acarbose compared with placebo (39 vs. 58%, P < 0.0001), the main reasons for noncompliance being flatulence (30 vs. 12%, P < 0.0001) and diarrhea (16 vs. 8%, P < 0.05). Analysis by intention to treat showed that patients allocated to acarbose, compared with placebo, had 0.2% significantly lower median HbA1c at 3 years (P < 0.001). In patients remaining on their allocated therapy, the HbA1c difference at 3 years (309 acarbose, 470 placebo) was 0.5% lower median HbA1c (8.1 vs. 8.6%, P < 0.0001). Acarbose appeared to be equally efficacious when given in addition to diet alone; in addition to monotherapy with a sulfonylurea, metformin, or insulin; or in combination with more complex treatment regimens. No significant differences were seen in FPG, body weight, incidence of hypoglycemia, or frequency of major clinical events. CONCLUSIONS: Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes, irrespective of concomitant therapy for diabetes. Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects.
Clinical correlates of plantar pressure among diabetic veterans.
Authors: Ahroni J H , Boyko E J , Forsberg R C
Published: March 2007

OBJECTIVE: To assess the relationship between diabetes characteristics, medical history, foot deformity, sensory neuropathy, and plantar foot pressure. RESEARCH DESIGN AND METHODS: There were 517 subjects from a cohort of diabetic veterans enrolled in a prospective study of risk factors for foot complications who contributed 1,017 limbs for study. We interviewed subjects to collect data on demographics, diabetes characteristics, and medical history. A research nurse practitioner performed a directed physical exam of the lower extremities, assessing foot deformities and including quantitative sensory testing with a 5.07 monofilament. In-shoe foot-pressure measurements were obtained with F-scan insoles on subjects wearing their own footwear while walking 10 m at their usual pace. RESULTS: In univariate analyses, significant associations were seen between at least one measure of plantar pressure and body mass, sex, race, age, insulin use, certain foot deformities, plantar callus, and sensory neuropathy. Diabetes duration, HbA1c, and history of foot ulcer or amputation were unrelated to plantar pressure. In multiple regression analyses, body mass measured as log (weight), insulin use, white race, male sex, plantar callus, and diabetes duration were significantly related to certain pressures. Foot deformities were related primarily to forefoot pressures. With high pressure at two or more sites defined as the outcome, only body mass remained statistically significant as a predictor of this outcome in a backwards elimination logistic regression model. CONCLUSIONS: High in-shoe plantar pressure in diabetic subjects can be predicted in part from readily available clinical characteristics. The mechanisms by which these characteristics may be related to plantar pressure require further study.
Low birth weight, family history of diabetes, and glucose intolerance in Swedish middle-aged men.
Authors: Carlsson S , Persson P G , Alvarsson M , Efendic S , Norman A , Svanström L , Ostenson C G , Grill V
Published: March 2007

OBJECTIVE: To investigate the association between low birth weight and glucose intolerance in relation to family history of diabetes. RESEARCH DESIGN AND METHODS: We conducted a population-based cross-sectional study of 2,237 men born in 1938-1957 in four municipalities in the outskirts of Stockholm, 50% of whom had a family history of diabetes (at least one first-degree or two second-degree relatives with diabetes). Oral glucose tolerance testing detected 35 cases of type 2 diabetes, 102 cases of impaired glucose tolerance, and 57 cases of impaired fasting glucose. RESULTS: In subjects without a family history of diabetes, low (< or = 3,000 g) birth weight was associated with an odds ratio of 2.3 (95% confidence intervals = 0.4-14.4) for diabetes, 1.8 (0.7-4.3) for impaired glucose tolerance, and 3.3 (1.0-10.4) for impaired fasting glucose. In subjects with a family history of diabetes, the corresponding figures were approximately similar, except for diabetes, for which the odds ratio was 5.4 (2.0-14.9). For men with low birth weight in combination with a family history of diabetes, the odds ratio was 10.9 (2.9-41.2) for diabetes, 2.4 (1.1-5.6) for impaired glucose tolerance, and 5.9 (2.1-16.3) for impaired fasting glucose. CONCLUSIONS: This study indicated that low birth weight is associated with type 2 diabetes, impaired glucose tolerance, and impaired fasting glucose in men. This finding was most pronounced in subjects with diabetes in the family, but it was also indicated in those without a family history of diabetes. Men with the combination of low birth weight and family history of diabetes seem to be at particularly high risk of developing type 2 diabetes.
Prevalence of "syndrome X" features in parents of type 1 diabetic patients with or without nephropathy.
Authors: Verhage B , Vervoort G , Wolkotte C , Elving L D , Wetzels J F , Willems H , Smits P , Verbeek A L , Berden J H
Published: March 2007

OBJECTIVE: To compare the prevalence of "syndrome X"-related parameters in parents of type 1 diabetic patients with diabetic nephropathy (DNP) to those in parents of diabetic patients without DNP. RESEARCH DESIGN AND METHODS: In this cross-sectional study, we included 50 parents of type 1 diabetic patients with DNP and 50 parents of diabetic patients without DNP. All parents were investigated in a fasting state for serum lipids including nonesterified fatty acids (NEFAs), glucose, HbA1c, plasma uric acid, fasting insulin levels, and albuminuria. Blood pressure was recorded in the supine position using an automatic device; ankle/brachial index was measured with Doppler ultrasound. Presence of cardiovascular disease was determined by a standardized questionnaire and electrocardiogram registration. Subjects without known diabetes underwent a 2-h oral glucose tolerance test. Anthropometric parameters such as BMI, waist-to-hip ratio, and percentage of body fat were measured. In addition to univariate analysis, a syndrome X score (SXS) was formulated, comprising a number of syndrome X-related biochemical, physiological, and/or anthropometric parameters. RESULTS: Univariate analysis revealed no significant differences in syndrome X parameters between parents of type 1 diabetic patients with or without DNP. Also, the composite SXS was similar in both groups. CONCLUSIONS: In this study, no differences were found in the prevalence of syndrome X features between parents of type 1 diabetic patients with DNP and parents of patients without DNP.
Depressive symptoms and occurrence of type 2 diabetes among Japanese men.
Authors: Kawakami N , Takatsuka N , Shimizu H , Ishibashi H
Published: March 2007

OBJECTIVE: To examine the relationship between depressive symptoms and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: In 1984, 2,764 male employees of an electrical company in Japan completed a self-administered questionnaire including the Zung Self-Rating Depression Scale (SDS). They were followed for the next 8 years, and 2,380 (86%) responded to the follow-up survey in 1992. During the follow-up survey, occurrence of type 2 diabetes was diagnosed according to World Health Organization criteria. RESULTS: A total of 41 cases of type 2 diabetes were identified during the 8-year follow-up survey. After controlling for other known risk factors for type 2 diabetes, a proportional hazard analysis indicated that subjects who had moderate or severe levels of depressive symptoms (> or = 48 on the SDS) at baseline had a 2.3 times higher risk of having type 2 diabetes at the follow-up survey than those who were not depressed (< or = 39 on the SDS) (P < 0.05). CONCLUSIONS: Depressive symptoms may be associated with the onset of type 2 diabetes.
Type 2 diabetes: incremental medical care costs during the first 8 years after diagnosis.
Authors: Brown J B , Nichols G A , Glauber H S , Bakst A W
Published: March 2007

OBJECTIVE: To describe and analyze the time course of medical care costs caused by type 2 diabetes, from the time of diagnosis through the first 8 postdiagnostic years. RESEARCH DESIGN AND METHODS: From electronic health maintenance organization (HMO) records, we ascertained the ongoing medical care costs for all members with type 2 diabetes who were newly diagnosed between 1988 and 1995. To isolate incremental costs (costs caused by the diagnosis of diabetes), we subtracted the costs of individually matched HMO members without diabetes from costs of members with diabetes. RESULTS: The economic burden of diabetes is immediately apparent from the time of diagnosis. In year 1, total medical costs were 2.1 times higher for patients with diabetes compared with those without diabetes. Diabetes-associated incremental costs (type 2 diabetic costs minus matched costs for people without diabetes) averaged $2,257 per type 2 diabetic patient per year during the first 8 postdiagnostic years. Annual incremental costs varied relatively little over the period but were higher during years 1, 7, and 8 because of higher-cost hospitalizations for causes other than diabetes or its complications. CONCLUSIONS: For the first 8 years after diabetes diagnosis, patients with type 2 diabetes incurred substantially higher costs than matched nondiabetic patients, but those high costs remained largely flat. Once the growth in costs due to general aging is controlled for, it appears that diabetic complications do not increase incremental costs as early as is commonly believed. Additional research is needed to better understand how diabetes and its diagnosis affect medical care costs over longer periods of time.
Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients.
Authors: Toft-Nielsen M B , Madsbad S , Holst J J
Published: March 2007

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore sought to evaluate the effect of infusion of GLP-1 for 48 h in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We infused GLP-1 (2.4 pmol.kg-1.min-1) or saline subcutaneously for 48 h in randomized order in six patients with type 2 diabetes to evaluate the effect on appetite during fixed energy intake and on plasma glucose, insulin, glucagon, postprandial lipidemia, blood pressure, heart rate, and basal metabolic rate. RESULTS: The infusion resulted in elevations of the plasma concentrations of intact GLP-1 similar to those observed after intravenous infusion of 1.2 pmol.kg-1.min-1, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration, whereas glucagon levels were unchanged. Neither triglycerides nor free fatty acids were affected. GLP-1 administration decreased hunger and prospective food intake and increased satiety, whereas fullness was unaffected. No side effects during GLP-1 infusion were recorded except for a brief cutaneous reaction. Basal metabolic rate and heart rate did not change significantly during GLP-1 administration. Both systolic and diastolic blood pressure tended to be lower during the GLP-1 infusion. CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure.
Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes.
Authors: Matyka K A , Crowne E C , Havel P J , Macdonald I A , Matthews D , Dunger D B
Published: March 2007

OBJECTIVE: To examine counterregulatory responses during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 29 prepubertal patients with type 1 diabetes underwent two overnight profiles. Data were analyzed from 16 children (median [range] 8.7 [5.9-12.9] years of age) with a night of hypoglycemia and a nonhypoglycemic night. Children hypoglycemic (< 3.5 mmol/l) on night 1 were given 25% extra carbohydrate as uncooked cornstarch with their usual evening snack on night 2 to avoid hypoglycemia. Glucose, growth hormone, and cortisol were measured every 15 min, catecholamines every 30 min, and glucagon, pancreatic polypeptide, insulin, and ketones every 60 min. A group of 15 healthy control subjects, aged 9.5 (5.6-12.1) years, underwent one overnight profile. RESULTS: Median duration of hypoglycemia was 225 (30-630) min, and glucose nadir was 2.0 (1.2-3.3) mmol/l. Insulin levels were not different on the two nights (P = 0.9, analysis of variance), but children with diabetes had higher insulin levels than normal control subjects between 2300 and 0300, maximal at 0200 (mean +/- SEM 57.4 +/- 5.7 vs. 31.6 +/- 5.0 pmol/l, P = 0.002). Peak epinephrine was higher on the night of hypoglycemia (0.98 [0.52-2.09] nmol/l) versus nonhypoglycemia (0.32 [0.21-0.62] nmol/l), P = 0.001, but norepinephrine (1.29 [1.07-2.64] vs. 1.26 [1.04-1.88] nmol/l, P = 0.5), glucagon (93 [64.2-125.6] vs. 100.5 [54.6-158] ng/l, P = 0.6), pancreatic polypeptide (410.2 [191-643.2] vs. 270.8 [158.2-777.8] ng/l, P = 0.5), and cortisol (513 [300-679] vs. 475 [235-739] nmol/l, P = 0.6) were not different. Glucose threshold for epinephrine release was very low, 1.9 +/- 0.2 mmol/l. There was a short-lived rise in growth hormone from 75-105 min after onset of hypoglycemia, maximal at 90 min (7.8 +/- 1.2 vs. 3.5 +/- 0.9 ng/ml, P = 0.02). CONCLUSIONS: The prolonged nature of nocturnal hypoglycemic episodes may be explained in part by defective counterregulation. The risk of nocturnal hypoglycemia needs to be reduced before intensification of insulin therapy can be contemplated in this age-group.
Circadian blood pressure during the early course of type 1 diabetes. Analysis of 1,011 ambulatory blood pressure recordings in 354 adolescents and young adults.
Authors: Holl R W , Pavlovic M , Heinze E , Thon A
Published: March 2007

OBJECTIVE: Little information is available on the early course of hypertension in type 1 diabetes. The aim of our study, therefore, was to document circadian blood pressure profiles in patients with a diabetes duration of up to 20 years and relate daytime and nighttime blood pressure to duration of diabetes, BMI, insulin therapy, and HbA1c. RESEARCH DESIGN AND METHODS: Ambulatory profiles of 24-h blood pressure were recorded in 354 pediatric patients with type 1 diabetes (age 14.6 +/- 4.2 years, duration of diabetes 5.6 +/- 5.0 years, follow-up for up to 9 years). A total of 1,011 profiles were available for analysis from patients not receiving antihypertensive medication. RESULTS: Although daytime mean systolic pressure was significantly elevated in diabetic subjects (+3.1 mmHg; P < 0.0001), daytime diastolic pressure was not different from from the height- and sex-adjusted normal range (+0.1 mmHg, NS). In contrast, both systolic and diastolic nighttime values were clearly elevated (+7.2 and +4.2 mmHg; P < 0.0001), and nocturnal dipping was reduced (P < 0.0001). Systolic blood pressure was related to overweight in all patients, while diastolic blood pressure was related to metabolic control in young adults. Blood pressure variability was significantly lower in girls compared with boys (P < 0.01). During follow-up, no increase of blood pressure was noted; however, diastolic nocturnal dipping decreased significantly (P < 0.03). Mean daytime blood pressure was significantly related to office blood pressure (r = +0.54 for systolic and r = +0.40 for diastolic pressure); however, hypertension was confirmed by ambulatory blood pressure measurement in only 32% of patients with elevated office blood pressure. CONCLUSIONS: During the early course of type 1 diabetes, daytime blood pressure is higher compared with that of healthy control subjects. The elevation of nocturnal values is even more pronounced and nocturnal dipping is reduced. The frequency of white-coat hypertension is high among adolescents with diabetes, and ambulatory blood pressure monitoring avoids unnecessary antihypertensive treatment.
Effect of hyperketonemia on plasma lipid peroxidation levels in diabetic patients.
Authors: Jain S K , McVie R , Jackson R , Levine S N , Lim G
Published: March 2007

OBJECTIVE: This study was undertaken to examine the effect of ketosis on plasma lipid peroxidation levels in diabetic patients. RESEARCH DESIGN AND METHODS: Plasma levels of lipid peroxidation products (malondialdehyde) and ketone bodies (acetoacetate and beta-hydroxybutyrate) were determined in diabetic patients (n = 70) and age-matched normal volunteers (n = 25). Diabetic patients with total ketone body levels > 1.0 mmol/l were considered hyperketonemic, and those with levels < or = 1.0 mmol/l were considered normoketonemic. RESULTS: After normalization versus total lipids, levels of lipid peroxidation were significantly higher in the plasma of hyperketonemic diabetic patients (P < 0.05), but not in normoketonemic diabetic patients, compared with age-matched normal volunteers. In addition, low ketonemia was associated with lower lipid peroxidation levels when lipid peroxidation and ketonemia were determined in the same patient (n = 7) at two different clinic visits. CONCLUSIONS: This study demonstrated an association between hyperketonemia and increased lipid peroxidation levels in diabetic patients, which suggests that ketosis is a risk factor in the elevated lipid peroxidation levels associated with diabetes. Further investigation is needed to determine whether antioxidant supplementation can be particularly beneficial in reducing lipid peroxidation and complications in type 1 diabetic patients who frequently encounter ketosis.
Increased urinary transferrin excretion predicts microalbuminuria in patients with type 2 diabetes.
Authors: Kazumi T , Hozumi T , Ishida Y , Ikeda Y , Kishi K , Hayakawa M , Yoshino G
Published: March 2007

OBJECTIVE: We studied whether increased urinary transferrin excretion rates (TERs) (urinary transferrin-to-urinary creatinine ratio > or = 107 micrograms/mmol, which is the sum of an average and 2 SDs in 431 healthy nondiabetic individuals) would predict the development of microalbuminuria (urinary albumin-to-urinary creatinine ratio > or = 2.8 mg/mmol) in patients with type 2 diabetes and normal urinary albumin excretion rates (AERs) (albumin-to-creatinine ratio < 2.8 mg/mmol). We also studied the influence of blood pressure, glycemic control, and serum levels of lipids and apolipoproteins on the later development of microalbuminuria. RESEARCH DESIGN AND METHODS: In 77 diabetic patients with normal AER, AER and TER were measured at baseline and after 24 months of follow-up. Blood pressure, glycemic control, and serum levels of lipids and apolipoproteins were measured at 1- to 2-month intervals during the follow-up period. RESULTS: Of the 16 patients who initially had increased TER, 5 (31%) developed microalbuminuria. In contrast, of the 61 who initially had normal TER, 4 (7%) developed microalbuminuria (P = 0.016). At baseline, no difference was found in age, sex, diabetes duration, diabetic medications, prevalence of hypertension, blood pressure, HbA1c levels, or serum lipid and apolipoprotein concentrations between the two group of patients with normal and increased TER. There was also no difference in duration of hypertension and prevalence of users of ACE inhibitors between two subgroups of hypertensive patients with normal and increased TER. During the 24 month follow-up period, those whose condition progressed to microalbuminuria had increased serum levels of triglycerides (1.87 +/- 0.49 vs. 1.29 +/- 0.64 mmol/l, P = 0.003) and apolipoprotein B (114 +/- 20 vs. 102 +/- 24 mg/dl, P = 0.05) and tended to have increased HbA1c levels (7.7 +/- 1.0 vs. 7.1 +/- 1.1%, P = 0.10) compared with those in whom microalbuminuria did not develop. Blood pressure, however, did not differ. In multivariate stepwise logistic regression analysis, the association between increased TER at baseline and subsequent development of microalbuminuria was significant (odds ratio 7.04 [95% CI 1.02-48.5], P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and normal AER, increased TER may predict the development of microalbuminuria and abnormalities in triglyceride-rich lipoprotein metabolism, and poor glycemic control may be associated with this progression.
Bone mineral density in patients with type 1 and type 2 diabetes.
Authors: Tuominen J T , Impivaara O , Puukka P , Rönnemaa T
Published: March 2007

OBJECTIVE: To assess the effect of type 1 and type 2 diabetes and insulin treatment on bone mineral density (BMD) in middle-aged and elderly men and women. RESEARCH DESIGN AND METHODS: We measured BMD and evaluated known determinants of osteoporosis in 56 type 1 and 68 type 2 diabetic patients and 498 nondiabetic community control subjects. All patients, aged 52-72 years, developed diabetes after the age of 30 years (i.e., after achievement of peak bone mass) and were treated with insulin. BMD was measured at the proximal femur with dual-energy X-ray absorptiometry. RESULTS: Among both sexes, BMD values were significantly lower in type 1 diabetic patients than in type 2 diabetic patients or the control subjects. When adjusted for age and BMI, the differences between type 1 diabetic patients and control subjects remained essentially unchanged in both sexes, whereas the differences between type 1 and type 2 diabetic subjects were significant only in men. After further adjustments for confounding factors, the average BMD values were still lower in type 1 diabetic subjects than in type 2 diabetic subjects although with lesser significance. Past low-energy fractures were more common in type 1 diabetic women than in type 2 diabetic women. CONCLUSIONS: The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes. This cannot be explained by insulin treatment, which was prescribed for both types of patients. Because the causes of low BMD in type 1 diabetes are unknown, these patients should be evaluated for the risk of osteoporosis and related fractures and offered appropriate preventive measures.
Use of a plastic insulin dosage guide to correct blood glucose levels out of the target range and for carbohydrate counting in subjects with type 1 diabetes.
Authors: Kaufman F R , Halvorson M , Carpenter S
Published: March 2007

OBJECTIVE: To improve glycemic control, a hand-held plastic Insulin Dosage Guide was developed to correct blood glucose levels outside of the target range. RESEARCH DESIGN AND METHODS: Protocol 1: Some 40 children (mean age 10.6+/-4.6 years) were randomly assigned for 3 months to use a written-on-paper algorithm or the Insulin Dosage Guide to correct abnormal blood glucose levels. Mean HbA1c and blood glucose levels and time to teach insulin dosage correction were compared. Protocol 2: The Insulin Dosage Guide was used by 83 subjects (mean age 11.4+/-4.3 years) for 1 year, and mean HbA1c levels, blood glucose levels, and number of consecutive high blood glucose values taken before and after the year were compared. Protocol 3: Some 20 patients (mean age 10.1+/-3.7 years) using rapid-acting insulin and 64 patients (mean age 15.9+/-3.6 years) using an insulin pump and rapid-acting insulin used the Insulin Dosage Guide and had mean blood glucose levels, HbA1c, and percentage of blood glucose levels outside of the target range determined. RESULTS: Protocol 1: There was a significant reduction in mean HbA1c (P = 0.04) and blood glucose levels (P = 0.05) and in the time needed to teach how to correct blood glucose values using the Insulin Dosage Guide compared with the paper algorithm. Protocol 2: There was a decrease in mean HbA1c levels (P = 0.0001) and a decrease in the mean number of consecutive blood glucose levels (P = 0.001) over the 1-year time period. Protocol 3: With rapid-acting insulin, there was a significant increase in the percentage of blood glucose levels within the target range (1 month, P = 0.04; at 3 months, P = 0.03). With the insulin pump, there was a high rate (90%) of blood glucose levels in the target range during pump initiation when the Insulin Dosage Guide was used. CONCLUSIONS: This inexpensive hand-held plastic card, which is portable and easy to use, may help patients improve glycemia and successfully manage diabetes.
Weight change and duration of overweight and obesity in the incidence of type 2 diabetes.
Authors: Wannamethee S G , Shaper A G
Published: March 2007

OBJECTIVE: To examine the relationship between weight change and duration of overweight and obesity and the incidence of type 2 diabetes in a cohort of middle-aged British men. RESEARCH DESIGN AND METHODS: We carried out a prospective study of cardiovascular disease in men aged 40-59 years at screening (1978-1980), drawn from one general practice in 24 British towns, who completed a postal questionnaire 5 years later (Q5) and for whom data on BMI at year 1 (Q1) and Q5 were available (n = 7,100). Men with diabetes at Q1 or Q5 and men with hyperglycemia at Q1 were excluded from the study (n = 184). The main outcome measure was type 2 diabetes (physician-diagnosed) during a mean follow-up period of 12 years starting at Q5 (1983-1985). RESULTS: In the 6,916 men with no history or evidence of diabetes, there were 237 incident cases of type 2 diabetes during the mean follow-up period of 12 years, a rate of 3.2/1,000 person-years. Substantial weight gain (>10%) was associated with a significant increase in risk of type 2 diabetes compared with that in men with stable weight (relative risk [RR] 1.61 [95% CI 1.01-2.56]) after adjustment for age, initial BMI, and other risk factors. Excluding men who developed diabetes within 4 years after the period of weight change increased the risk further (1.81 [1.09-3.00]). After adjustment and exclusion of men who developed diabetes early in the follow-up, weight loss (> or =4%) was associated with a reduction in the risk of type 2 diabetes, compared with that in the stable group, that reached marginal significance (0.65 [0.42-1.03], P = 0.07). A test for trend that fitted weight change as a continuous covariate showed the risk of diabetes to increase significantly from maximum weight loss to maximum weight gain (P = 0.0009). The lower risk associated with weight loss was seen in obese (> or =28 kg/m2) and nonobese subjects and in men with normal (<6.1 mmol/l) and high (> or =6.1 mmol/l) nonfasting blood glucose levels. Although not statistically significant, this is consistent with a benefit from weight loss. Risk of type 2 diabetes increased progressively and significantly with increasing levels of initial BMI and also with the duration of overweight and obesity (P<0.0001). CONCLUSIONS: This study confirms the critical importance of overweight and obesity, particularly of long duration, in the development of type 2 diabetes. The data support current public health recommendations to reduce the risk of type 2 diabetes by preventing weight gain in middle-aged men who are not overweight and by encouraging weight loss in overweight and obese men.
Association between stress and glycemic control in adults with type 1 (insulin-dependent) diabetes.
Authors: Lloyd C E , Dyer P H , Lancashire R J , Harris T , Daniels J E , Barnett A H
Published: March 2007

OBJECTIVE: To examine the relationship between stressful life events and alterations in glycemic control in adults with diabetes. RESEARCH DESIGN AND METHODS: The occurrence of stressful experiences was recorded using the life Events and Difficulties Schedule of Brown and Harris in 55 adults with type 1 diabetes. The two most recent measures of glycemic control (HbA1c) were obtained from medical records, with poor glycemic control defined by the sample median (> or =7.7%). RESULTS: Subjects whose control deteriorated over time or who remained in poor glycemic control were significantly more likely to report severe personal stressors (SPS) in the month before HbA1c measurement, compared with subjects whose control remained fair or whose control improved (43 and 25% vs. 7 and 0%; P = 0.000). Subjects whose control remained fair or whose control improved were significantly more likely to report only positive life events during the same time period (80 and 11% vs. 0 and 0%, respectively; P = 0.000). Multiple regression analysis demonstrated that SPS, sex, and lack of further education were all significantly associated with either remaining in poor control or deterioration of control. CONCLUSIONS: The study has shown that recent severe stressors are associated with poorer glycemic control. Positive life events were associated with fair or improved glycemic control. This study has its limitations, and future studies should be prospective in design. While it is not always possible to avoid stress, learning to recognize and cope with stressors may help individuals with diabetes maintain good glycemic control and improve overall quality of life.
Early identification of diabetic foot ulcers that may require intervention using the micro lightguide spectrophotometer.
Authors: Rajbhandari S M , Harris N D , Tesfaye S , Ward J D
Published: March 2007

OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ulcers, but hypoxia has also been shown to be a potent stimulus for growth. There are no studies looking specifically at ulcer oxygen levels during the healing process. We measured the serial microvascular oxygen saturation (SaO2) of the foot ulcer, the ulcer margin, and a control site using the Erlangen micro lightguide spectrophotometer (EMPHO II; Bodenseewerk Geratetechnik, Erlangen, Germany) to study serial changes during healing. RESEARCH AND DESIGN METHODS: Studied over 9 months were 14 patients with neuropathy with a total of 24 foot ulcer sites. Of these patients, four (seven ulcers) had significant ischemia as determined by the ankle-brachial pressure index (ABPI) and transcutaneous oxygen tension. RESULTS: Of 21 ulcer sites with serial measurements, only 13 ulcers healed. In those ulcers, a significant reduction (P<0.05) in SaO2 occurred with healing. SaO2 dropped from 58% at initial presentation (mean area 2.6 cm2) to 47% at midsize (mean area 1.2 cm2 at 5.2 weeks) and finally reduced to 45% just before it healed. Similar trends were also seen around the margin of the ulcers (initial 49%, midsize 45%, and final 41%; P = 0.1). However, there were no such changes on the control sites (43, 40, and 40%; P = 0.5) or within the eight ulcers that did not heal (46, 42, and 53%; P = 0.2). CONCLUSIONS: Serial microvascular oxygen measurements may be used to identify at an early stage those ulcers that are unlikely to heal and, therefore, need surgical intervention.
Insulin sensitivity in African-American children with and without family history of type 2 diabetes.
Authors: Danadian K , Balasekaran G , Lewy V , Meza M P , Robertson R , Arslanian S A
Published: March 2007

OBJECTIVE: African-Americans are at increased risk for type 2 diabetes. We have previously demonstrated that African-American children are hyperinsulinemic and insulin resistant compared with their white American peers. The aim of the present investigation was to assess the impact of family history of type 2 diabetes on insulin sensitivity in African-American children. RESEARCH DESIGN AND METHODS: A total of 13 prepubertal healthy children with negative family history (FH-) and 9 with positive family history (FH+) of type 2 diabetes underwent a 3-h hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp study to assess insulin sensitivity. The groups were comparable for age, pubertal status, total body adiposity determined by dual-energy X-ray absorptiometry, abdominal adiposity assessed by computed tomography scan at the level of L4-5 lumbar vertebra, and physical fitness measured by maximal oxygen consumption (VO2max). RESULTS: The FH+, compared with the FH-, group had lower insulin-stimulated glucose disposal (10.9+/-1.2 vs. 14.2+/-0.9 mg x kg(-1) x min(-1), P = 0.035) and lower nonoxidative glucose disposal (5.7+/-0.8 vs. 8.3+/-0.6 mg x kg(-1) x min(-1), P = 0.015), with no differences in rates of glucose oxidation, fat oxidation, or insulin-mediated free fatty acid suppression. Fasting hepatic glucose production assessed with [6,6-2H2]glucose and basal rates of glucose and fat oxidation were not different between the two groups. CONCLUSIONS: These data suggest that in African-American children, family history of type 2 diabetes is a risk factor for insulin resistance. These children manifest important metabolic alterations, including impaired insulin-stimulated total and nonoxidative glucose disposal early in the first decade of life. We propose that this familial tendency, combined with environmental influences, could lead to type 2 diabetes decades later.
Predictors of change in the neuropsychological profiles of children with type 1 diabetes 2 years after disease onset.
Authors: Northam E A , Anderson P J , Werther G A , Warne G L , Andrewes D
Published: March 2007

OBJECTIVE: To identify type 1 diabetes-related predictors of change in the neuropsychological profiles of children over the first 2 years of the illness. RESEARCH DESIGN AND METHODS: Children (n = 116) aged 3-14 years were assessed soon after diagnosis and re-evaluated 2 years later to examine relationships between illness variables, such as age of onset and metabolic control history, and changes in neuropsychological status over the first 2 years of type 1 diabetes. RESULTS: Illness variables were significant predictors of change in neuropsychological test scores within 2 years of onset of type 1 diabetes. Age of onset of type 1 diabetes predicted negative change on Performance Intelligence Quotient, whereas both recurrent severe hypoglycemia and chronic hyperglycemia were associated with reduced memory and learning capacity. CONCLUSIONS: These results suggest that the relationship between metabolic control and neuropsychological risk is nonlinear in that children with either recurrent severe hypoglycemia or chronically elevated blood sugars exhibit negative changes in their neuropsychological profiles. Onset of type 1 diabetes very early in life adds another dimension of risk, particularly affecting the acquisition of visuospatial skills.