bluuebunny/crossref_metadata_2025 huggingface dataset:
The Trp64Arg Polymorphism of the β3-Adrenergic Receptor Gene: Lack of association with NIDDM and features of insulin resistance syndrome
Authors: Rissanen Johanna , Kuopusjärvi Marja , Pihlajamäki Jussi , Sipiläinen Raisa , Heikkinen Sami , Vanhala Mauno , Kekäläinen Päivi , Kuusisto Johanna , Laakso Markku
Published: March 2007

OBJECTIVE

To investigate the association of the Trp64Arg polymorphism of the β3-adrenergic receptor gene with NIDDM and the features of insulin resistance syndrome in subjects from eastern Finland.

RESEARCH DESIGN AND METHODS

We determined the prevalence of the Trp64Arg polymorphism of the β3-adrenergic receptor gene by restriction fragment length polymorphism analysis in 110 patients with NIDDM (54 men and 56 women, age 63 ± 1 years, BMI 30.4 ± 0.5 kg/m2), in 183 patients with features of insulin resistance syndrome (103 men and 80 women, age 44 ± 0 years, BMI 31.1 ± 0.4 kb/m2), and in 82 normoglycemic control men (age 54 ± 1 years, BMI 26.3 ± 0.4 kg/m2).

RESULTS

The allele frequency of the Trp64Arg polymorphism of the β3-adrenergic receptor gene was similar in patients with NIDDM, in patients with insulin resistance syndrome, and in control subjects (0.08, 0.07, and 0.07, respectively; NS). In addition, this polymorphism was not associated with low resting metabolic rate, abdominal obesity, increased lipid oxidation, hypertension, or earlier development of NIDDM as previously described. Furthermore, in 82 normoglycemic male control subjects the Trp64Arg polymorphism was not associated with insulin resistance evaluated by the euglycemic-hyperinsulinemic clamp.

CONCLUSIONS

The Trp64Arg polymorphism of the beta β3-adrenergic receptor gene is unlikely to be a major genetic predisposer to NIDDM or insulin resistance syndrome in subjects from eastern Finland.
Evaluation of Skin Vasomotor Reflexes in Response to Deep Inspiration in Diabetic Patients by Laser Doppler Flowmetry: A new approach to the diagnosis of diabetic peripheral autonomic neuropathy
Authors: Aso Yoshimasa , Inukai Toshihiko , Takemura Yoshihiro
Published: March 2007

OBJECTIVE

To evaluate the peripheral sympathetic function in feet of NIDDM patients by means of laser Doppler flowmetry.

RESEARCH DESIGN AND METHODS

After deep inspiration, we measured the vasoconstrictor response in the feet of 51 patients with NIDDM, as compared with those of 20 healthy control subjects, using laser Doppler flowmetry. Subjects whose skin temperature was < 32°C were excluded from our study because a skin temperature of ∼ 34°C is the optimal temperature for the evaluation of skin vasomotor reflexes in response to a deep inspiration by laser Doppler flowmetry.

RESULTS

The vasoconstrictor response to deep inspiration in the big toe was significantly decreased in NIDDM patients compared with healthy subjects (26.8 ± 2.0 vs. 48.3 ± 18.5%, P < 0.0001). In NIDDM patients, the vasoconstrictor response was positively correlated with the duration of diabetes, the median motor and sensory nerve conduction velocities, the coefficient of variation of the R-R interval at rest, and the postural fall in systolic blood pressure. The vasoconstriction was inversely correlated with the vibratory perception threshold.

CONCLUSIONS

Vasomotor reflexes in the lower limbs were markedly impaired in NIDDM patients. The measurement of vasoconstrictor responses to deep inspiration by using laser Doppler flowmetry is a novel and useful method for detecting peripheral sympathetic failure in diabetic patients.
Glomerular Hyperfiltration Is Associated With Blood Pressure Abnormalities in Normotensive Normoalbuminuric IDDM Patients
Authors: Pecis Miriam , Azevedo Mirela J , Gross Jorge L
Published: March 2007

OBJECTIVE

To analyze the blood pressure patterns in normoalbuminuric IDDM patients with glomerular hyperfiltration.

RESEARCH DESIGN AND METHODS

A controlled cross-sectional study of 38 normotensive normoalbuminuric (urinary albumin excretion rate <20 μg/min) IDDM patients (18 hyperfiltering [glomerular filtration rate >134 ml · min−1 · 1.73 m−2] and 20 normofiltering) and 20 normal individuals matched for age, sex, and BMI was performed. The 24-h ambulatory blood pressure was monitored using an auscultatory technique (Pressurometer IV, Del Mar Avionics), the glomerular filtration rate was measured by 51Cr-labeled EDTA method, extracellular volume by the distribution volume of 51Cr-labeled EDTA, and the 24-h urinary albumin excretion rate by radioimmunoassay.

RESULTS

Mean nocturnal diastolic blood pressure was higher in hyperfiltering IDDM patients (70.4 ± mmHg), when compared with the control group (65.1 ± 5.3 mmHg, P = 0.04). Diastolic blood pressure night:day ratio was higher in hyperfiltering IDDM patients (92.0 ± 8.6%), when compared with normofiltering IDDM patients (85.9 ± 4.8%) and control subjects (87.0 ± 6.8%, P = 0.02). In IDDM patients, the glomerular filtration rate significantly correlated with the diastolic blood pressure night:day ratio (r = 0.5, P = 0.002), extracellular volume (r = 0.04, P = 0.002), and HbA1 (r = 0.3, P = 0.03). In stepwise multiple regression analysis, factors associated with glomerular filtration rate were diastolic blood pressure night:day ratio, extracellular volume, and HbA1 (adjusted r2 = 0.27, P = 0.003).

CONCLUSIONS

Glomerular hyperfiltration is associated with higher nocturnal diastolic blood pressure and with a blunted nocturnal decrease in diastolic blood pressure levels in normotensive and normoalbuminuric IDDM patients.
Induction of Long-Term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients by Transient Intensive Insulin Treatment
Authors: Ilkova Hasan , Glaser Benjamin , Tunçkale Aydin , Bagriaçik Nazif , Cerasi Erol
Published: March 2007

OBJECTIVE

Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in β-cell function. Hyperglycemia per se has deleterious effects on both beta-cell function and insulin action, which are partially reversible by the short-term control of blood glucose levels. We hypothesized that the induction of euglycemia, using intensive insulin therapy at the time of clinical diagnosis, could lead to a significant improvement in insulin secretion and action and thus alter the clinical course of the disease.

RESEARCH DESIGN AND METHODS

Thirteen newly diagnosed diet-unresponsive type 2 diabetic patients were treated with continuous subcutaneous insulin infusion (CSII) for 2 weeks and followed longitudinally while being treated with diet alone.

RESULTS

Four patients were considered therapeutic failures since CSII failed to induce euglycemia (n = 1) or glucose control deteriorated within 6 months after CSII (n = 3). The remaining nine patients were maintained on diet alone with adequate control from 9 to > 50 months (median ± SE, 26 ± 4.8 months). In five patients, glycemic control deteriorated after 9–36 months, but a repeat 2-week CSII treatment reestablished control in four patients. One of these patients underwent a third CSII treatment 13 months later. At the time this article was written, six patients of the initial group were still controlled without medication 16–59 months (median ± SE, 45.5 ± 6.6 months) after the initiation of treatment. Body weight remained unchanged in all patients.

CONCLUSIONS

These findings suggest that in a significant proportion of type 2 diabetic patients who fail to respond to dietary measures, short-term intensive insulin treatment can effectively establish responsiveness, allowing long-term glycemic control without medication. Further studies are required to establish whether simpler treatment regimens could be equally effective. If the hypothesis offered here finds support, present approaches to the management of newly diagnosed type 2 diabetes may need to be revised.
Coronary Artery Disease in Diabetic Patients With Lower-Extremity Arterial Disease: Disease Characteristics and Survival: A report from the Coronary Artery Surgery Study (CASS) registry
Authors: Barzilay Joshua I , Kronmal Richard A , Bittner Vera , Eaker Elaine , Evans Campbell , Foster Eric D
Published: March 2007

OBJECTIVE

Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD.

RESEARCH DESIGN AND METHODS

A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were ≥ 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time.

RESULTS

Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality.

CONCLUSIONS

Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.
Power Spectral Analysis of Heart Rate Variability in Children and Adolescents With IDDM
Authors: Wawryk Andrew M , Bates David J , Couper Jennifer J
Published: March 2007

OBJECTIVE

To investigate power spectral analysis (PSA) of heart rate variability (HRV) in children and adolescents with IDDM, its relationship with other measures of HRV and standard cardiovascular responses, and factors associated with reduced HVR.

RESEARCH DESIGN AND METHODS

A total of 130 subjects with IDDM aged 12.8 ± 3.2 years and 108 healthy control subjects were studied. Power spectra were analyzed from supine electrocardiograph (ECG) recordings by processing into consecutive R-R intervals and analysis using fast Fourier transformation. Standard cardiovascular responses to deep breathing and standing were performed.

RESULTS

IDDM subjects had a reduction in total power including both low-frequency (0.05–0.14 Hz; P = 0.0001) and high-frequency (0.14–0.40 Hz; P = 0.0002) components. These changes were seen from diagnosis. Other measures of HRV, coefficient of variation (CV) and standard deviation (SD) of mean resting heart rate, were also significantly lower in IDDM. All 20 (15%) of the 130 IDDM subjects with total power < the 5th percentile in control subjects also had reduced HRV when measured by CV of heart rate. There was an independent relationship between age and the high-frequency component in IDDM subjects and control subjects. Total power correlated with mean heart rate (r = −0.56; P < 0.0001), CV of heart rate (r = 0.90; P < 0.00001), SD of heart rate (r = 0.91; P < 0.00001), heart rate response to deep breathing (r = 0.45; P < 0.0001), and duration in IDDM subjects. There was no correlation with short-term or long-term metabolic control. Retesting of 27 subjects showed a variability in total power and its components comparable to other measures of HRV and standard heart rate responses.

CONCLUSIONS

Changes in HRV are a sensitive and reproducible measure of early autonomic dysfunction in childhood. In this age-group, PSA appears no more sensitive a measure of reduced HRV than other closely correlated measures of HRV.
Dermal Interstitial Glucose as an Indicator of Ambient Glycemia
Authors: Service F John , O'Brien Peter C , Wise Steven D , Ness Sheryl , LeBlanc Suzanne M
Published: March 2007

OBJECTIVE

Using a novel minimally invasive (≤ 1.4 mm) technique to sample minuscule (0.5 microliter) amounts of dermal interstitial fluid (ISF), we assessed the accuracy of its glucose concentrations in predicting concurrently measured venous plasma and capillary plasma glucose concentrations.

RESEARCH DESIGN AND METHODS

A total of 67 adult (37 male and 30 female) volunteers (57 with and 10 without diabetes) with venous plasma glucose levels from 1.6 to 28.4 mmol/l underwent forearm ISF, antecubetal venous, and fingertip capillary sampling.

RESULTS

Rank correlations were 0.974 for ISF 1 vs. 2, 0.954 for ISF vs. venous, 0.935 for ISF vs. capillary, and 0.987 for venous vs. capillary. Median absolute differences were 0.53 mmol/l for ISF 1 vs. 2, 1.33 mmol/l for ISF vs. venous, 1.06 mmol/l for ISF vs. capillary, and 0.56 mmol/l for capillary vs. venous. Equations expressing ISF glucose as a function of venous and capillary glucose and equations expressing capillary glucose as a function of venous glucose had slopes of 0.995, 0.936, and 1.021, respectively (none significantly different from unity), and intercepts of 1.03 mmol/l (P = 0.024), 0.94 mmol/l (P = 0.131), and 0.56 mmol/l (P = 0.041), respectively. Error grid analysis of ISF vs. venous glucose and of capillary vs. venous glucose showed that 97% of the measurements fell within grids A and B.

CONCLUSIONS

Dermal ISF sampling is a bloodless minimally invasive technique that provides a medium for glucose measurement, the concentrations of which closely reflect ambient glycemia to a degree comparable with that of capillary glucose measurements.
Role of IGF Binding Protein- 1 in the Dawn Phenomenon and Glycemic Control in Children and Adolescents With IDDM
Authors: Kobayashi Kisho , Amemiya Shin , Sawanobori Emi , Higashida Kosuke , Ishihara Toshihide , Kobayashi Koji , Kato Kiyohiko , Nakazawa Shinpei
Published: March 2007

OBJECTIVE

To clarify the involvement of IGF binding protein (IGFBP)-1 in the dawn rise in plasma glucose and in the overall glycemic control in patients with IDDM.

RESEARCH DESIGN AND METHODS

Seventy patients with IDDM were divided into three groups according to pubertal development. Blood samples were obtained for measuring plasma glucose, IGFBP-1, and free insulin at 2200, 0500, and 0700 over a 2-day period. Levels of HbA1c, IGF-1, and IGFBP-3 were determined at 0700. Urinary growth hormone (GH) was collected overnight. To examine its frequency, the dawn phenomenon was defined on the basis of the following: 1) change in plasma glucose from 0500 to 0700, 2) plasma glucose level at 0700, and 3) no antecedent hypoglycemia.

RESULTS

There was a statistically significant link between the dawn changes in plasma glucose and IGFBP-1 (r = 0.37, P < 0.01). The former was not related to the change in free insulin or to the overnight urinary GH level. In stepwise regression analyses, plasma glucose at 0700 = 0.03 IGFBP-1 (P < 0.01) + 0.525 HbA1c (P < 0.01) + 3.696 (R2 = 51%). Approximately half of the patients in each group exhibited the dawn phenomenon; 38% of patients with HbA1c < 8% also showed the dawn phenomenon.

CONCLUSIONS

We have demonstrated a statistically significant link between the morningrisk in IGFBP-1 and plasma glucose. The free fraction of IGF-1 modulated by acute changes in IGFBP-1 may play a direct role. The dawn phenomenon may occur regardless of pubertal stage or glycemic control in children and adolescents with IDDM.
Effects of Glycemic Control on Plasma 3-Deoxyglucosone Levels in NIDDM Patients
Authors: Hamada Yoji , Nakamura Jiro , Fujisawa Hiroki , Yago Hisashi , Nakashima Eltaro , Koh Naoki , Hotta Nlgishi
Published: March 2007

OBJECTIVE

To clarify the effects of glycemic control on the level of 3-deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic patients.

RESEARCH DESIGN AND METHODS

Fasting plasma samples were collected from 15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six poorly controlled patients before and after improved glycemic control for at least 2 months. Plasma 3-DG was determined by high-performance liquid chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the relationship of 3-DG levels with plasma glucose or HbA1c levels and examined changes in 3-DG levels after glycemic control in the six patients.

RESULTS

Plasma 3-DG was significantly more increased in diabetic patients than in nondiabetic control subjects (31.8 ± 11.3 vs. 12.8 ± 5.2 ng/ml, means ± SD, P < 0.001), but there was an ∼ threefold difference in 3-DG levels among diabetic patients. 3-DG levels were well correlated with plasma glucose (r = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabeticpatients. The improvement of hyperglycemia in six patients resulted in a significant decrease in 3-DG (35.2 ± 13.2 vs. 21.3 ±3.4 ng/ml, P < 0.05).

CONCLUSIONS

The results indicate that the plasma glucose level is a predominant determinant of the plasma 3-DG level in diabetic patients and good glycemic control would be important to reduce this reactive metabolite.
Effects of Lisinopril and Nifedipine on the Progression to Overt Albuminuria in IDDM Patients With Incipient Nephropathy and Normal Blood Pressure
Authors: Crepaldi Gaetano , Carta Quirico , Deferrari Giacomo , Mangili Ruggero , Navalesi Renzo , Santeusanio Fausto , Spalluto Antonio , Vanasia Alessandro , Villa G Marco , Nosadini Romano ,   The Italian Microalbuminuria Study Group in IDDM
Published: March 2007

OBJECTIVE

Intervention trials on renal function in IDDM patients with microalbuminuria (MA) should adopt the rate of decline of glomerular filtration rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA show no change in GFR over a follow-up period of 10 years. Thus, in the present study, we used the cumulative incidence of progression to albuminuria (albumin excretion rate [AER] > 200 μ/min) from MA as the primary endpoint and the yearly increase in AER at a rate of 50% above baseline as the secondary end-point of renal function.

RESEARCH DESIGN AND METHODS

Ninety-two normotensive IDDM patients underwent double-blind, double-dummy treatment with either lisinopril or slow-release nifedipine in comparison with placebo. Ten patients discontinued the study during the 3-year follow-up period.

RESULTS

During the 3-year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril-treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis indicated a reduction in the risk of progression to macroalbuminuria of 58.1% (95% CI 27.8−68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95% CI 32.5−73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the 34 patients on placebo. Baseline AER was 71 μ/min (range: 20.7−187.3) in progressors and 73 μ/min (range: 20.2−174.1) in nonprogressors (NS). The percentage of patients who showed a > 50% yearly increase of AER above baseline values was significantly lower in the lisinopril group (13 of 32, 40.6%, P < 0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo group (23 of 34, 67.6%). The lisinopril group had significantly lower blood pressure values during follow-up than either the nifedipine (P < 0.05) or the placebo (P < 0.01) group.

CONCLUSIONS

Our data show that both lisinopril and nifedipine are effective in delaying the occurrence of macroalbuminuria in normotensive IDDM patients with MA. As overt proteinuria strongly predicts end-stage renal failure, both treatments appear capable of preventing such a complication in normotensive IDDM patients with MA. However, lisinopril appears more powerful in slowing the course of nephropathy.
Evaluation of a Self-Administered Sensory Testing Tool to Identify Patients at Risk of Diabetes-Related Foot Problems
Authors: Birke James A , Rolfsen Robert J
Published: March 2007

OBJECTIVE

To study the use of a self-administered sensory testing tool designed to identify individuals at risk for diabetes-related foot problems and determine the inter-rater reliability between patient and provider sensory evaluations.

RESEARCH DESIGN AND METHODS

Nine centers in eight states with established foot prevention centers mailed 196 self-screening testing materials to randomly selected patients with diabetes scheduled for follow-up appointments. Patients were instructed to perform a sensory test using a 10-g nylon filament at specified sites on the foot and to complete a brief survey form before their appointment. During the follow-up appointment, providers retested patients using an identical sensory filament at the same sites and completed a provider survey.

RESULTS

Of the patients, 145 kept their appointments and completed the self-screening materials. There were 141 patient and 137 provider surveys that indicated the instructions were clear and easy to use. Sixty-eight percent of the patients reported self-testing without the assistance of another person. Patient and provider sensory test findings disagreed (P = 0.0014) in 18 of 145 cases and fair inter-rater reliability was found (κ = 0.73). Disagreement in sensory tests was related to patient age (P = 0.012). Sensory loss, previously undetected by providers, was found in 23 case subjects.

CONCLUSIONS

Self-administered sensory tests provide patients an opportunity to share in the responsibility for preventing diabetes-related foot problems but should not replace routine foot evaluation by a provider.
Incidence and Progression of Diabetic Retinopathy in Hispanics and Non-Hispanic Whites With Type 2 Diabetes. San Luis Valley Diabetes Study, Colorado
Authors: Tudor Stephanie M , Hamman Richard F , Baron Anna , Johnson David W , Shetterly Susan M
Published: March 2007

OBJECTIVE

To learn if Hispanic people with type 2 diabetes have excess incidence and/or progression of diabetic retinopathy and to explore the association of risk factors with diabetic retinopathy.

RESEARCH DESIGN AND METHODS

There were 244 subjects with type 2 diabetes (65.3% Hispanic) with at least one follow-up visit between 1984 and 1992 examined for the development of retinopathy over a median of 4.8 years (range 2.0−6.6 years). Stereo fundus photos were graded by the University of Wisconsin Reading Center.

RESULTS

Of the 169 subjects without retinopathy at baseline, 47 developed some retinopathy, an incidence rate of 63.7 per 1,000 person-years (PY), or a 4-year cumulative incidence of 22.5%. The Hispanic incidence rate was 58.3/1,000 PY (95% CI: 39.4−83.3), which was lower than among non-Hispanic whites, 76.1/1,000 PY (44.3−121.9). Progression occurred in 24 of the 75 subjects with retinopathy at baseline, a 4-year cumulative rate of 24.1%. Logistic regression showed that insulin treatment was associated with higher risk of any retinopathy (odds ratio [OR] = 8.45, 2.65−26.97), and both systolic blood pressure (odds ratio [OR] = 1.58, 0.99−2.52) and total GHb (OR = 1.46, 0.99−2.17) nearly attained statistical significance. After adjustment for multiple potential risk factors, the Hispanic/non-Hispanic white OR was 0.66 (0.28−1.57).

CONCLUSIONS

No excess risk for incident retinopathy was found among Hispanic compared with non-Hispanic white subjects in this population. These results are consistent with our previously reported prevalence data from the same population but differ from reports of excess prevalence among Texas Hispanics. No other Hispanic incidence data are available to assist in reconciling this difference.
Study of Genetic Prediabetic South Indian Subjects: Importance of hyperinsulinemia and β-cell dysfunction
Authors: Snehalatha C , Ramachandran A , Satyavani K , Latha E , Viswanathan Vijay
Published: March 2007

OBJECTIVE

To study 1) whether abdominal adiposity was present in adult offspring of two NIDDM parents, 2) whether abdominal adiposity was associated with the development of glucose intolerance, and 3) the association of pancreatic β-cell function with impaired glucose tolerance (IGT) and NIDDM in these groups.

RESEARCH DESIGN AND METHODS

One hundred offspring whose parents both had NIDDM were studied (60 men, 40 women, mean age 34 ± 6.9 years, BMI 27.4 ± 4.1 kg/m2). None had a history of glucose intolerance. Nondiabetic control subjects with no family history of diabetes were also studied for comparison (21 men, 19 women, age 36 ± 10.3 years, BMI 26 ± 3.7 kg/m2). A standard oral glucose tolerance test was done for all, and plasma glucose, C-peptide, and insulin responses were measured. Abdominal fat measurements at L4-L5 were made using a computed axial tomography scan. Subcutaneous fat (SF), visceral fat (VF), and total fat (TF) areas were measured and VF/SF ratio was calculated. An index of insulin secretion (Δ I/G) was derived as the ratio of incremental insulin at 30 min divided by 30-min plasma glucose.

RESULTS

IGT was detected in 32 offspring and diabetes in 21 offspring. Diabetic men had a higher TF area than the other groups. SF, VF, and VF/SF ratios were similar in control men and in offspring with normal glucose tolerance (NGT), IGT, or diabetes. Among control subjects, women had significantly lower VF than men. Female offspring had higher VF than the control subjects, but intragroup variations were absent. Fasting insulin and all C-peptide responses were higher in NGT compared with control subjects (P < 0.02). The 2-h insulin and C-peptide responses were higher in IGT subjects (P < 0.005). In diabetic subjects, the insulin-to-glucose ratio, C-peptide-to-glucose ratio, and Δ I/G were significantly low compared with all other groups (P < 0.005). Multiple logistic regression analysis showed that the area of insulin response had a positive association and Δ I/G had a negative association with diabetes, while age, sex, BMI, waist-to-hip ratio, abdominal fat areas, fasting and 2-h insulin, area of insulin, and the C-peptide measurements did not show independent associations. Two-hour insulin showed a positive association with IGT, while increasing area of insulin showed a negative association.

CONCLUSIONS

Visceral adiposity seemed to precede glucose intolerance only in women, but it had no independent association with IGT or NIDDM. Insulin resistance, indicated by higher plasma insulin response, and insulin secretory defect, indicated by low Δ I/G at 30 min, were associated with diabetes. β-cell defect was not independently associated with IGT. Increased abdominal visceral adiposity does not appear to be a prerequisite for development of IGT or diabetes in Asian Indians with a strong genetic predisposition for diabetes.
Effects of a Monounsaturated Fatty Acid–Enriched Hypocaloric Diet on Cardiovascular Risk Factors in Obese Patients With Type 2 Diabetes
Authors: Gumbiner Barry , Low Cecilia C , Reaven Peter D
Published: March 2007

OBJECTIVE

To determine whether the lipoprotein response to weight loss in obese patients with type 2 diabetes can be improved by modifying the macronutrient composition of the commonly prescribed low-fat, high-carbohydrate (CHO) hypocaloric diet.

RESEARCH DESIGN AND METHODS

Nine obese patients with type 2 diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight-reducing formula diet and compared with eight obese patients with type 2 diabetes treated with a low-fat, high-CHO weight-reducing formula diet. Weight loss ensued for 6 weeks, followed by 4 weeks of refeeding using isocaloric formulas enriched with MUFA or CHO, respectively. Fasting blood samples were obtained to measure plasma lipoproteins and LDL susceptibility to oxidation (measured as lag time: time required to induce in vitro formation of conjugated dienes).

RESULTS

At baseline, there were no differences between the groups in plasma lipids, lipoproteins, or LDL susceptibility to oxidation. Weight loss was similar between the groups. Dieting resulted in decreases in total plasma cholesterol, LDL, HDL, triglycerides, and apolipoproteins A and B (P < 0.05), but the MUFA group manifested a greater decrease in total cholesterol, triglycerides, and apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO group (P < 0.05). Improvements in these parameters were sustained during refeeding. After dieting, lag time was prolonged in the MUFA group (208 ± 10 min) compared with the CHO group (146 ± 11 min; P < 0.05). Lag time was prolonged further during refeeding in the MUFA group (221 ± 13 min, P = 0.10), while the CHO group remained unchanged (152 ± 9 min, P < 0.05). Lag time correlated strongly with the oleic acid content of LDL after dieting and refeeding (r = 0.74 and r = 0.93, respectively; both P < 0.001).

CONCLUSIONS

Macronutrient content is an important determinant of the lipoprotein response to weight loss in obese patients with type 2 diabetes. MUFA-enriched hypocaloric diets potentiate the beneficial effects of weight loss to ameliorate cardiovascular risk factors in obese patients with type 2 diabetes.
Acute Metabolic Response to High-Carbohydrate, High-Starch Meals Compared With Moderate-Carbohydrate, Low-Starch Meals in Subjects With Type 2 Diabetes
Authors: Gannon Mary C , Nuttall Frank Q , Westphal Sydney A , Fang Sean , Ercan-Fang Nacide
Published: March 2007

OBJECTIVE

The monosaccharides resulting from the digestion of ingested carbohydrates are glucose, fructose, and galactose. Of these three monosaccharides, only ingested glucose resulted in a large increase in the plasma glucose concentration. Fructose (Metabolism 41:510–517, 1992) and galactose (Metabolism 42:1560–1567, 1993) had only a minor effect. Therefore, we were interested in determining whether we could design a mixed meal, using foods of known monosaccharide, disaccharide, and starch composition, the ingestion of which would result in only a small rise in plasma glucose concentration.

RESEARCH DESIGN AND METHODS

The experimental meal was composed of very little readily digestible starch but rather large amounts of fruits and vegetables. It contained 43% carbohydrate, 22% protein, and 34% fat. The results were compared with a second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat, with an emphasis on complex carbohydrates (starch). It also was compared with a third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of that consumed by the average American. The test meals were ingested in random order by people with type 2 diabetes who were not treated with oral hypoglycemic agents or insulin. Each subject ingested each type of meal. The same identical meal was ingested at 0800, 1200, and 1700.

RESULTS

The integrated 24-h plasma glucose area response was statistically significantly smaller (P < 0.05) after ingestion of the low-starch meals compared with the high-starch, highcarbohydrate meals or the typical American meals. The 24-h integrated serum insulin area response also was statistically significantly less (P < 0.05) after ingestion of the low-starch meals compared with the high-starch meals or the typical American meals. The serum triglyceride area response was similar after ingestion of all three test diets.

CONCLUSIONS

A diet in which fruits, nonstarch vegetables, and dairy products are emphasized may be useful for people with type 2 diabetes.
Birth Weight, Adult Weight, and Girth as Predictors of the Metabolic Syndrome in Postmenopausal Women: The Rancho Bernardo Study
Authors: Yarbrough Donald E , Barrett-Connor Elizabeth , Kritz-Silverstein Donna , Wingard Deborah L
Published: March 2007

OBJECTIVE

Recent studies have demonstrated an association between low birth weight and chronic and metabolic disorders in adulthood such as type 2 diabetes, hypertension, and dyslipidemia. These disorders tend to cluster in a condition known as the metabolic syndrome (syndrome X). Only two studies have reported an association of birth weight to the metabolic syndrome. The present study is distinguished as the only study to focus on postmenopausal women.

RESEARCH DESIGN AND METHODS

Subjects were 303 community-dwelling, postmenopausal Caucasian women aged 50–84 years. Metabolic and anthropometric variables were measured at a clinic visit; birth weight was assessed by self-report on a mailed questionnaire.

RESULTS

The metabolic syndrome, defined as the simultaneous presence of hypertension, dyslipidemia, and abnormal glucose tolerance, was present in 7.9% of these women. Compared with women in the highest birth weight tertile (8.1–13.0 lb, mean 9.4 lb), those in the lowest birth weight tertile (2.5–6.8 lb, mean 5.5 lb) exhibited an increased prevalence (12.0 vs. 4.3%, P < 0.05) and 2.41 times the risk (95% CI 1.06–5.51) of developing the metabolic syndrome. Women with a heavy birth weight had an increased risk of adult obesity. Nevertheless, women in the lowest birth weight tertile who became adults in the highest tertile of BMI (>25.2 kg/m2) or waist circumference (>80.7 cm) had the highest prevalence of the metabolic syndrome (∼30%).

CONCLUSIONS

Low birth weight coupled with adult obesity is a strong determinant of the metabolic syndrome in postmenopausal women.
Islet Cell Antibodies Are Less Predictive of IDDM Among Unaffected Children in the General Population Than in Sibs of Children With Diabetes
Authors: Knip Mikael , Karjalainen Jukka , Åkerblom Hans K ,   The Childhood Diabetes in Finland Study Group
Published: March 2007

OBJECTIVE

To examine the controversial issue of whether islet cell antibodies (ICAs) have a higher predictive value for progression to clinical IDDM in first-degree relatives of patients with diabetes than in the general population.

RESEARCH DESIGN AND METHODS

ICAs were analyzed with standard immunofluorescence in two population-based groups: 765 sibs of children with recent-onset diabetes and 1,212 unaffected Finnish children <20 years of age at initial screening. Those positive for ICAs were additionally tested for antibodies to GAD (GADAs) and the protein tyrosine phosphatase-related 1A-2 antigen (IA-2As). Subsequently, these subjects were observed for the manifestation of clinical IDDM over the next 7 years.

RESULTS

The frequency of both detectable ICAs and ICA levels ≥20 Juvenile Diabetes Foundation units (JDF U) was significantly higher among the sibs than in the general population (7.8 vs. 4.1% and 4.8 vs. 2.0%, respectively; P < 0.001). The prevalence of GADAs (37/60 vs. 3/48; P < 0.001) and IA-2As (31/60 vs. 0/48; P < 0.001) was increased among ICA-positive sibs compared with ICA-positive individuals from the background population. Over the next 7 years, 24 sibs (3.1%) and 3 unrelated children positive for ICAs (0.3%) progressed to clinical diabetes. The positive predictive value of ICAs was thus 6% in the general population and 40% among the sibs (P < 0.001), or 13 and 59%, respectively (P < 0.001), with an antibody cutoff level of 20 JDF U. The positive predictive value was related to the number of positive autoantibodies in sibs, which was 57% in those with three antibodies, 50% in those with two antibodies, and only 6% in those with ICAs alone.

CONCLUSIONS

These data show that the frequency of multiple autoantibodies is substantially lower in ICA-positive children representing the general population than in ICA-positive sibs of children with IDDM. As a consequence, the predictive value of ICAs for IDDM is higher in sibs of affected children than in the general population. This finding must be taken into account when planning intervention trials aimed at preventing or delaying the manifestation of clinical diabetes in individuals from the general population who test positive for ICAs.
Meta-Analysis of the Effect of Insulin Lispro on Severe Hypoglycemia in Patients With Type 1 Diabetes
Authors: Brunelle Rocco L , Llewelyn Julie , Anderson James H , Gale Edwin A M , Koivisto Veikko A
Published: March 2007

OBJECTIVE

A precise time-action profile of insulin lispro (Humalog) at mealtime may reduce the incidence of severe hypoglycemia. Because it is a rare complication, we performed a cumulative meta-analysis to compare the frequency of severe hypoglycemia during insulin lispro and human regular insulin therapy in type 1 diabetic patients.

RESEARCH DESIGN AND METHODS

The analysis included eight large multicenter clinical trials, three with parallel and five with crossover designs. The studies included 2,576 type 1 diabetic patients in total, with 2,327 receiving insulin lispro and 2,339 receiving regular human insulin, representing >1,400 patient-years of insulin therapy. Severe hypoglycemia was defined as coma or requiring glucagon or intravenous glucose. The patients received either NPH or ultralente as their basal insulin and insulin lispro or regular human insulin before each meal.

RESULTS

Seventy-two patients (3.1%) had a total of 102 severe hypoglycemic episodes during insulin lispro therapy, compared with 102 patients (4.4%) with a total of 131 episodes during regular human insulin therapy (P = 0.024).

CONCLUSIONS

The results of this meta-analysis demonstrate that in type 1 diabetic patients, the frequency of severe hypoglycemia can be reduced by taking insulin lispro as compared with regular human insulin therapy.
Differential Glucose Tolerance in Dipper and Nondipper Essential Hypertension: The implications of circadian blood pressure regulation on glucose tolerance in hypertension
Authors: Chen Jaw-Wen , Jen Shu-Long , Lee Wen-Lieng , Hsu Nai-Wei , Lin Shing-Jong , Ting Chih-Tai , Chang Mau-Song , Wang Ping H
Published: March 2007

OBJECTIVE

The goals of this study were to compare glucose tolerance in dipper and nondipper hypertensive patients and to explore the cause of glucose intolerance in essential hypertension.

RESEARCH DESIGN AND METHODS

A total of 50 patients <45 years old who had essential hypertension were recruited and studied by 24-h blood pressure monitoring and an oral glucose tolerance test (OGTT). Autonomic function was assessed with spectral analysis of heart rate variability.

RESULTS

Dipper hypertensive patients (n = 25) had lower nocturnal blood pressure than nondipper (n = 25) patients. During OGTT, postprandial glucose levels were higher in the nondippers at 0,90, and 120 min (all P < 0.05). Nondippers had a higher fasting insulin/glucose ratio than was apparent in normal control subjects. Despite higher postprandial glucose levels, nondippers had lower postprandial insulin levels. These results suggest that nondippers were insulin resistant and that their pancreatic β-cell function was impaired. For all patients, nocturnal reduction of blood pressure was inversely related to total glucose levels under the OGTT curve and was positively related to postprandial insulin levels. Daytime heart rate did not differ between the dippers and nondippers, but nocturnal heart rate was higher in the nondippers, suggesting that nocturnal sympathetic activities were higher among the nondippers. Spectral analysis of heart rate variability suggests that the nondippers had lower parasympathetic activities and unbalanced sympathetic/parasympathetic outflow.

CONCLUSIONS

These findings indicate that nondipper hypertensive patients are more glucose intolerant than are dipper patients. The abnormalities of glucose metabolism in nondippers could be explained by insulin resistance and β-cell dysfunction. The results of spectral analysis suggest that abnormal autonomic outflow may represent a possible link between hypertension and associated metabolic dysfunction.
Islet cell autoimmunity in white and black children and adolescents with IDDM.
Authors: Libman I M , Pietropaolo M , Trucco M , Dorman J S , LaPorte R E , Becker D
Published: March 2007

OBJECTIVE: To compare the frequency of islet cell antibodies (ICA) and antibodies to GAD65 and IA-2(ICA512) between black and white children and adolescents at the diagnosis of IDDM in a large consecutive series of cases from Children's Hospital of Pittsburgh. RESEARCH DESIGN AND METHODS: ICA and antibodies to GAD65 and IA-2 were measured in 437 white and black children and adolescents who were diagnosed with IDDM at < 19 years of age at Children's Hospital of Pittsburgh from January 1983 to December 1985, from January to December 1989, and from January 1996 to December 1997. RESULTS: The prevalence of ICA(H), GAD65, and IA-2 antibodies was significantly lower in blacks than whites at onset of the disease. In contrast, the prevalence of ICA(R) alone was higher in blacks. None of the antibodies were present in 12% of the blacks compared with 4% in whites. The same pattern was seen in both sexes. The prevalence of antibodies in white patients with onset of IDDM at <11 years of age was no different than in those who developed IDDM during adolescence. In contrast, black patients showed a significantly lower prevalence of almost all antibodies in the adolescent group. CONCLUSIONS: Black adolescents were more likely to not have antibodies, suggesting either that they have a nonautoimmune type of diabetes or that antibodies are not being detected by these assays.
Decrease in glomerular filtration rate in Japanese patients with type 2 diabetes is linked to atherosclerosis.
Authors: Taniwaki H , Nishizawa Y , Kawagishi T , Ishimura E , Emoto M , Okamura T , Okuno Y , Morii H
Published: March 2007

OBJECTIVE: We assessed the effects of atherosclerosis on the glomerular filtration rate (GFR) in patients with type 2 diabetes and who had micro- or normoalbuminuria. RESEARCH DESIGN AND METHODS: A total of 61 Japanese patients with type 2 diabetes were recruited from inpatients of Osaka City University Hospital. They ranged in age from 40 to 69 years (28 men and 33 women). Each subject collected a 24-h urine sample for quantitative analysis of albumin. Absence of albuminuria was defined as a urinary albumin excretion level of <30 mg/24 h (n = 36) and microalbuminuria as a level of 30-300 mg/24 h. The GFR was estimated using 99mTc diethylenetriamine pentaacetic renogram method. As indexes of atherosclerosis, we measured the intimal-medial thickness (IMT) and distensibility of the carotid artery using high-resolution B-mode ultrasonagraphy and an echo-tracking system. We measured the resistance index (RI) of the renal interlobar arteries by pulsed Doppler sonography. RESULTS: The clinical characteristics of type 2 diabetic patients with and without microalbuminuria did not differ except for duration of diabetes, which was longer in the patients with microalbuminuria. GFR also did not differ between the patients with and without microalbuminuria. GFR was significantly correlated with the patient's age (r = -0.256, P < 0.05), carotid IMT (r = -0.326, P < 0.05), carotid stiffness beta (r = -0.449, P < 0.001), and renal arterial RI (r = -0.365, P < 0.05). In multiple regression analysis, independent factors associated with GFR were carotid IMT (R2 = 0.108, P = 0.0102), carotid stiffness beta (R2 = 0.208, P = 0.0003), and renal artery RI (R2 = 0.130, P = 0.0043). CONCLUSIONS: The decline in GFR in type 2 diabetic patients in the early stages of nephropathy may be due in part to atherosclerosis.
Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis.
Authors: Niskanen L , Turpeinen A , Penttilä I , Uusitupa M I
Published: March 2007

OBJECTIVE: We studied the 15-year cardiovascular mortality and morbidity of newly diagnosed patients with type 2 diabetes and of nondiabetic control subjects and the predictors of cardiovascular mortality in diabetic patients. RESEARCH DESIGN AND METHODS: We performed a 15-year prospective study of 133 middle-aged patients with newly diagnosed type 2 diabetes and 144 control subjects. Cardiovascular risk factors were assessed in both groups at baseline and after 5 and 10 years. RESULTS: Total mortality was markedly higher in patients with type 2 diabetes (total: 44.3 vs. 12.9% for men, age-adjusted odds ratio [OR] 5.0, P < 0.001; 44.4 vs. 11.0% for women, OR 5.2, P < 0.001), which was due to increased cardiovascular mortality (ORs for men and women: 6.2 and 11.2, respectively, P < 0.001 for both). The incidences of fatal and nonfatal myocardial infarction and stroke were likewise higher in diabetic patients. In univariate analyses and various multiple logistic regression analyses, hyperglycemia was a constant predictor of cardiovascular mortality assessed at the time of diagnosis or at 5- or 10-year examinations. Moreover, lipoprotein abnormalities characteristic of type 2 diabetes (low HDL cholesterol, high LDL triglycerides or apolipoprotein B levels, and low LDL cholesterol/apolipoprotein B ratio as a marker for LDL size) were predictive of cardiovascular death in these analyses. CONCLUSIONS: This long-term study of a well-characterized group of newly diagnosed patients strengthens the view that the prognosis in middle-aged subjects is markedly impaired and that both hyperglycemia and compositional lipoprotein abnormalities are predictors of cardiovascular mortality in patients with type 2 diabetes.
A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.
Authors: Goldberg R B , Einhorn D , Lucas C P , Rendell M S , Damsbo P , Huang W C , Strange P , Brodows R G
Published: March 2007

OBJECTIVE: The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33). Patients underwent 6 weeks of dose adjustment followed by 12 weeks of dose maintenance. Fasting and stimulated glycosylated hemoglobin (HbA1c), plasma glucose, insulin, and C-peptide were measured at predetermined intervals. Adverse events and hypoglycemic episodes were recorded. RESULTS: From baseline to last visit, mean HbA1c decreased from 8.5 to 7.8% in patients treated with repaglinide and increased from 8.1 to 9.3% in patients receiving placebo, with a statistically significant difference of - 1.7% (P < 0.0001) between treatment groups at the last visit. Mean fasting plasma glucose and postprandial glucose increased in patients receiving placebo and decreased in patients treated with repaglinide, with statistically significant (P < 0.01) differences between groups at the last visit. Concentrations of fasting and postprandial insulin and C-peptide were lower at the last visit compared with baseline for patients treated with placebo and higher for patients treated with repaglinide, and the differences between groups were statistically significant (P < 0.05). Overall, repaglinide was well tolerated. CONCLUSIONS: This study demonstrated that repaglinide was safe and efficacious in lowering blood glucose concentrations. In addition to overall improvement in glycemic control noted with repaglinide in both sulfonylurea-treated patients and oral hypoglycemic agent-naive patients, repaglinide had a potent glucose-lowering effect in the postprandial period.