bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Antibody Response to a Short Course of Human Insulin Therapy in Women With Gestational Diabetes
Authors: Balsells Montserrat , Corcoy Rosa , Mauricio Dídac , Morales Josefa , García-Patterson Apolonia , Carreras Gemma , Puig-Domingo Manuel , de Leiva Alberto
Published: March 2007

OBJECTIVE

To assess the insulin antibody (IA) response to human insulin (HI) therapy in women with gestational diabetes.

RESEARCH DESIGN AND METHODS

IAs were measured by a competitive radiobinding assay in 50 women with gestational diabetes before and during treatment with HI and after delivery. At delivery, 15 maternal-cord blood sample pairs were analyzed for IA. As a reference, we searched for IA in 25 new-onset type I diabetic patients, before and at 3, 6, and 12 months after insulin therapy.

RESULTS

Insulin autoantibodies (IAAs) were detected in 1 of 50 women with gestational diabetes and 4 of 16 type I diabetic patients (P < 0.05). At the end of pregnancy after 9.3 ± 6.8 weeks on insulin therapy, 22 of 50 (44%) women with gestational diabetes became IA+ and 4 additional women were found to be positive 2 months postpartum. After 3 months on insulin, type I diabetic patients showed a higher rate of IA positivity (92%, P < 0.001). IA titers at the end of pregnancy were associated with the cumulative insulin dose (r = 0.29, P < 0.05). Postpartum, IA disappeared slowly in most IA+ women, but two women still showed IA 2 years after delivery Titers in cord blood were strongly related to those in maternal blood (r = 0.74, P < 0.01). The rate of adverse fetal outcome did not differ in IA− and IA+ mothers (27 vs. 40%, NS).

CONCLUSIONS

HI is immunogenic, and a short course of HI therapy induces IA in ∼ 50% of women with gestational diabetes and 92% of type I diabetic patients. In women with gestational diabetes, insulin dose is slightly associated with IA titers. These IAs apparently cross the placenta. Fetal outcome does not differ according to the maternal IA status, and IAs disappear gradually after delivery but may remain positive for 2 years after delivery.
Glibenclamide, but Not Acarbose, Increases Leptin Concentrations Parallel to Changes in Insulin in Subjects With NIDDM
Authors: Haffner Steven M , Hanefeld Markolf , Fischer Sabine , Fuçker Katja , Leonhardt Wolfgang
Published: March 2007

OBJECTIVE

To hypothesize if glibenclamide, which increases insulin levels, also increases leptin concentrations.

RESEARCH DESIGN AND METHODS

Leptin is a hormone that regulates weight in mice. In obese humans, leptin concentrations are increased, suggesting resistance to the effects of this hormone. Although short-term infusion of insulin during the hyperinsulinemiceuglycemic clamp does not increase leptin concentration, the effect of oral antidiabetic agents on leptin concentration is unknown. Differing effects can be expected, since glibenclamide acts via stimulation of insulin secretion, whereas acarbose inhibits alpha-glucosidases of the small intestine and has no direct effect on insulin levels. We examined the effect of acarbose (n = 4), glibenclamide (n = 6), and placebo (n = 6) on insulin and leptin levels during 24-h periods before and after 16 weeks of therapy.

RESULTS

We observed a significant diurnal variation in leptin concentrations. This was inversely related to insulin levels during the 24-h follow-up with usual diet. Neither the placebo nor acarbose altered leptin concentrations. However, glibenclamide increased leptin concentrations parallel to insulin levels. There were only minor changes in body weight during the l6-week follow-up: decrease in the placebo group (change −0.5 kg/m2, P = 0.07) and acarbose (change −0.7 kg/m2, P = 0.046) and increase in the glibenclamide group (change 0.8 kg/m2, P = 0.27). However, individual subjects who gained weight had increases in their leptin concentrations. The diurnal variation in leptin concentrations was preserved after glibenclamide.

CONCLUSIONS

Glibenclamide increases circadian leptin and insulin concentrations, whereas acarbose does not. This observation may help to explain weight gain in subjects treated with glibenclamide and stable weight in those treated with acarbose in the long run.
Optimal Time of Administration of Insulin Lispro. Importance of meal composition
Authors: Strachan Mark W J , Frier Brian M
Published: March 2007

OBJECTIVE

To compare the glucodynamics of pre- and postprandial administration of insulin lispro using test meals of differing composition.

RESEARCH DESIGN AND METHODS

Twenty subjects with IDDM were studied on four separate occasions. Ten subjects ingested high-carbohydrate and high-fat breakfasts with a large liquid component, and 10 subjects ingested high-carbohydrate and high-fat breakfasts in a more solid form. With each meal, insulin lispro was injected 10 min preprandial on one occasion and 20 min postprandial on another. The magnitude and temporal pattern of postprandial glucose excursions were observed.

RESULTS

With all meal types studied, postprandial blood glucose excursions were significantly smaller when insulin lispro was administered preprandially (P < 0.05). With both high-carbohydrate meals and the liquid high-fat meal, preprandial administration of lispro was associated with modest postprandial increments of blood glucose. With the solid high-fat meal, preprandial lispro produced a cumulative decline in postprandial blood glucose, whereas blood glucose rose when lispro was administered postprandially.

CONCLUSIONS

For meals with a high carbohydrate content, the optimal time of administration of lispro is preprandial. However, for meals with a high solid fat content, postprandial administration of lispro may be preferable.
The Effect of the Insulin Analog Lispro on Nighttime Blood Glucose Control in Type 1 Diabetic Patients
Authors: Ahmed Abu Baker E , Home Philip D
Published: March 2007

OBJECTIVE

Unmodified regular insulin has a long absorption tail, unlike the fast-acting insulin analog lispro, and may contribute to hypoglycemia in the early part of the night. A randomized crossover double-blind study was performed to compare blood glucose concentrations in the early part of the night in type 1 diabetic patients receiving lispro or unmodified regular human insulin, in random order, on 2 separate study days.

RESEARCH DESIGN AND METHODS

We studied 23 C-peptide-negative patients; 12 were using a premeal plus basal insulin regimen, and 11 were using twice-daily insulin injections. Patients were admitted to the investigation unit at 5:00 P.M. and received a single dose of lispro or unmodified regular human insulin before the evening meal. In both groups, the NPH insulin dose remained unchanged. Identical meals and snacks were eaten at the same time during both study days.

RESULTS

Average postprandial (6:00−10:00 P.M.) blood glucose concentrations were significantly lower after lispro therapy compared with human insulin (7.1 ± 0.4 [SE] vs. 8.5 ± 0.4 mmol/l, P = 0.0002). Nighttime (midnight to 4:00 A.M.) blood glucose concentrations were significantly higher after lispro compared with human insulin (10.3 ± 0.4 vs. 9.1 ± 0.4 mmol/l, P = 0.02). This difference was greatest in patients on the premeal plus basal insulin regimen (11.6 ± 0.5 vs. 8.7 ± 0.4 mmol/l, P < 0.001). The incidence of nocturnal hypoglycemia (midnight to 4:00 A.M., blood glucose < 3.5 mmol/l) was less with lispro compared with unmodified insulin (1 vs. 6 patients, P = 0.04). Nighttime (midnight to 4:00 A.M.) 3-hydroxybutyrate (102 ± 13 vs. 51 ± 7 mumol/l, P = 0.000) and glycerol (52 ± 3 vs. 42 ± 2 mumol/l, P < 0.01) were significantly higher after lispro therapy compared with human insulin in patients on the premeal plus bolus insulin regimen.

CONCLUSIONS

Lispro can improve postprandial blood glucose control and reduce the incidence of nocturnal hypoglycemia at the expense of nocturnal hyperglycemia and hyperketonemia in patients using a premeal plus basal insulin regimen.
Serum Ferritin as a Component of the Insulin Resistance Syndrome
Authors: Fernández-Real José-Manuel , Ricart-Engel Wifredo , Arroyo Enric , Balançá Rafael , Casamitjana-Abella Roser , Cabrero Dolores , Fernández-Castañer Miquel , Soler Joan
Published: March 2007

OBJECTIVE

In epidemiological studies, serum ferritin was the second-strongest determinant of blood glucose (after BMI) in regression models and the third-strongest determinant of serum insulin (after BMI and age). Its concentration also correlated positively with plasma triglycerides and apolipoprotein B concentrations, and negatively with HDL2 cholesterol. We hypothesized that serum ferritin could be a marker of insulin resistance.

RESEARCH DESIGN AND METHODS

Oral glucose tolerance and insulin sensitivity (SI, minimal model method) were prospectively evaluated in 36 healthy subjects. The relationship between serum ferritin and metabolic control (as measured by HbA1c levels) was also studied in 76 consecutive NIDDM patients.

RESULTS

In healthy subjects, log-transformed serum ferritin (LOGFER) correlated with basal serum glucose (r = 0.44, P = 0.007), but not with BMI, age, systolic or diastolic blood pressure, total cholesterol, VLDL cholesterol, HDL cholesterol, total triglycerides, VLDL triglycerides, serum insulin, or HbA1c (all P = NS). Identical results were obtained when the two lowest quartiles of serum ferritin were evaluated separately. However, in the two highest quartiles, LOGFER correlated with BMI (0.50, P = 0.02), diastolic blood pressure (r = 0.8, P < 0.0001), serum LDL cholesterol (r = 0.57, P = 0.01), VLDL cholesterol (r = 0.48, P = 0.03), total cholesterol and HDL2 and HDL3 subtractions of HDL cholesterol (r = −0.68, −0.76, −0.55, P = 0.001. < 0.0001, and 0.01, respectively), total triglycerides (r = 0.60, P = 0.006), HDL2/HDL3 quotient (P = −0.71, P = 0.001), VLDL triglycerides (r = 0.65, P = 0.004), and serum uric acid (r = 0.51, P = 0.03), but not with systolic blood pressure (r = 0.38, P = 0.15). After adjusting for BMI, only the correlations between LOGFER and diastolic blood pressure (r = 0.7, P = 0.002) and HDL2/HDL3 quotient (r = −0.63, P = 0.01) remained significant. Strong correlations between LOGFER and glucose area under the curve during oral glucose tolerance test (Pearson's r = 0.73, P = 0.001) and S1 (r = −0.68, P = 0.001), which remained significant after controlling for BMI, were observed. LOGFER (β = −0.44, P = 0.01) and BMI (β = −0.52, P = 0.004) constituted independent predictors of insulin sensitivity in a multivariate analysis (R2 = 0.68). In 76 consecutive NIDDM outpatients, serum glucose (P < 0.00001) and LOGFER (P = 0.03) independently predicted the value of HbA1c (R2 = 0.40) in a multiple linear regression analysis.

CONCLUSIONS

The correlations among serum ferritin and diastolic blood pressure, HDL quotient, glucose area under the curve, and S1 suggest that serum ferritin could be a marker of the insulin resistance syndrome. Serum ferritin may also be an independent determinant of poor metabolic control in the diabetic patient.
Physical Activity, Dyspnea, and Chest Pain Before ana After Coronary Artery Bypass Grafting in Relation to a History of Diabetes
Authors: Herlitz Johan , Haglid Maria , Hartford Marianne , Karlson Björn W , Karlsson Thomas , Lindelöw Björn , Caidahl Kenneth
Published: March 2007

OBJECTIVE

To describe the limitation of physical activity and symptoms of chest pain and dyspnea before and after coronary artery bypass grafting (CABG) in relation to a history of diabetes.

RESEARCH DESIGN AND METHODS

All patients in western Sweden in whom CABG was performed between 1988 and 1991 were asked to complete a questionnaire before 3 months and 2 years after the operation. The questionnaire evaluated limitation of physical activity and symptoms of chest pain and dyspnea.

RESULTS

In all, 2,121 patients participated in the evaluation, of whom 13% had a history of diabetes. The overall 2-year mortality was 14% among patients with a history of diabetes and 6% among patients without such a history (P < 0.001). The proportion of patients with a limitation of physical activity caused by chest pain decreased from 76% before CABG to 19% 2 years after in diabetic patients (P < 0.001) and from 79 to 17% in nondiabetic patients (P < 0.001). The proportion of diabetic patients without dyspnea increased from 13% before to 31% 2 years after CABG (P < 0.001). The corresponding figures for nondiabetic patients were 12 and 43% (P < 0.001). Symptoms of angina pectoris were reported in 94% of diabetic patients before CABG versus 35% after 2 years (P < 0.001). Corresponding figures for nondiabetic patients were 93 and 29% (P < 0.001). Aggregate data confirmed differences between diabetic and nondiabetic patients, with more symptoms in the diabetic patients, particularly with regard to dyspnea.

CONCLUSIONS

Mortality during 2 years of follow up was more than twice as high in diabetic than in nondiabetic patients. Limitation of physical activity, dyspnea, and angina pectoris improved markedly and similarly in diabetic and nondiabetic patients after CABG. Whereas limitation of physical activity and dyspnea was more frequent in diabetic than in nondiabetic patients, the occurrence of angina pectoris was more similar in the two groups.
Effect of Continuous Subcutaneous Insulin Infusion With Lispro on Hepatic Responsiveness to Glucagon in Type 1 Diabetes
Authors: Launay Brigitte , Zinman Bernard , Tildesley Hugh D , Strack Thomas , Chiasson Jean-Louis
Published: March 2007

OBJECTIVE

People with type 1 diabetes frequently develop a blunted counterregulatory hormone response to hypoglycemia coupled with a decreased hepatic response to glucagon, and consequently, they have an increased risk of severe hypoglycemia. We have evaluated the effect of insulin lispro (Humalog) versus regular human insulin (Humulin R) on the hepatic glucose production (HGP) response to glucagon in type 1 diabetic patients on intensive insulin therapy with continuous subcutaneous insulin infusion (CSII).

RESEARCH DESIGN AND METHODS

Ten subjects on CSII were treated for 3 months with lispro and 3 months with regular insulin in a double-blind randomized crossover study. After 3 months of treatment with each insulin, hepatic sensitivity to glucagon was measured in each subject. The test consisted of a 4-h simultaneous infusion of somatostatin (450 μg/h) to suppress endogenous glucagon, regular insulin (0.15 mU · kg−1 · min−1), glucose at a variable rate to maintain plasma glucose near 5 mmol/l, and D-[6,6−2H2]glucose to measure HGP. During the last 2 h, glucagon was infused at 1.5 ng · kg−1 · min−1. Eight nondiabetic people served as control subjects.

RESULTS

During the glucagon infusion period, free plasma insulin levels in the diabetic subjects were 71.7 ± 1.6 vs. 74.8 ± 0.5 pmol/1 after lispro and regular insulin treatment, with plasma glucagon levels of 88.3 ± 1.8 and 83.7 ± 1.5 ng/1 for insulin:glucagon ratios of 2.8 and 3.0, respectively (NS). However, plasma glucose increased to 9.2 ± 1.1 mmol/l after lispro insulin compared with 7.1 ± 0.9 mmol/l after regular insulin (P < 0.01), and the rise in HGP was 5.7 ± 2.8 μmol · kg−1 · min−1 after lispro insulin versus 3.1 ± 2.9 μmol · kg−1 · min−1 after regular insulin treatment (P = 0.02). In the control subjects, HGP increased by 10.7 ± 4.2 μmol · kg−1 · min−1 under glucagon infusion.

CONCLUSIONS

Insulin lispro treatment by CSII was associated with a heightened response in HGP to glucagon compared with regular human insulin. This suggests that insulin lispro increases the sensitivity of the liver to glucagon and could potentially decrease the risk of severe hypoglycemia.
Determining true glomerular filtration status in newly presenting type 2 diabetic subjects using age and sex adjustment.
Authors: Playle R , Ollerton R L , Dunstan F D , Evans W D , Burch A , Luzio S D , Owens D R
Published: March 2007

OBJECTIVE: To determine age- and sex-adjusted reference ranges (ASARRs) for glomerular filtration status using data from nondiabetic subjects and to apply these to newly presenting type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Glomerular filtration rate corrected for body surface area (cGFR) was determined using a radionuclide (51Cr-EDTA) method in 75 non-diabetic subjects (37 men, 38 women) and 219 type 2 diabetic subjects (157 men, 62 women). The 95% constant reference ranges (CRRs) were calculated as mean nondiabetic cGFR+/-1.96 SD. The 95% ASARRs were calculated by Altman's method from the nondiabetic cGFR versus age regression residuals for both male and female subjects. RESULTS: Using Altman's method, the intercepts, but not the gradients, of the cGFR versus age regressions were significantly different between male and female subjects (intercept difference [95% CI] 8.2 [1.3-15.1], gradient difference -0.4 [-1.1 to 0.3]). Fitting a common gradient, 95% ASARRs for normofiltration were found to be from 123.9 - (0.89 X age) to 181.7 - (0.89 x age) for male subjects, and from 116.0 - (0.89 X age) to 173.2 - (0.89 X age) for female subjects. The 95% CRR for normofiltration was 70.2-138.1 ml x min(-1) x (1.73 m)(-2). When applied to the diabetic cGFRs, the CRRs and ASARRs gave, respectively, 17% (37/219) versus 21% (46/219) hyperfiltrators and 83% (181/219) versus 79% (172/219) normofiltrators. Using the ASARRs, 14 normofiltrators (6 men, 8 women) were reclassified as hyperfiltrators (change [n/total n] [95% CI] 8% [14/181] [4-12]), and 5 hyperfiltrators (5 men, 0 women) were reclassified as normofiltrators (change 14% [5/37] [5-30]). CONCLUSIONS: We conclude that age and sex adjustment are essential to assess glomerular filtration status.
Increased plasma pancreastatin-like levels in gestational diabetes: correlation with catecholamine levels.
Authors: Sánchez-Margalet V , Lobón J A , González A , Fernández-Soto M L , Escobar-Jiménez F , Goberna R
Published: March 2007

OBJECTIVE: To investigate plasma pancreastatin (a chromogranin A-derived peptide) and catecholamine levels (counterregulatory hormones) in subjects with gestational diabetes compared with normal pregnant subjects. RESEARCH DESIGN AND METHODS: Fasting blood samples were obtained from 11 normal pregnant and 12 nonobese gestational diabetic subjects at late pregnancy (30+/-1 weeks). Selection criteria were those recommended by the National Diabetes Data Group (modified from O'Sullivan original criteria). Plasma glucose, insulin, glucagon, pancreastatin-like, epinephrine, and norepinephrine were measured. RESULTS: Gestational diabetic subjects had significantly higher insulin levels than control pregnant subjects (18+/-1 vs. 15+/-1 microU/ml), whereas glucose and glucagon levels where comparable in the two groups. However, increased catecholamine levels (epinephrine and norepinephrine) were found in the gestational diabetic group. We also found increased pancreastatin-like levels in these patients compared with the pregnant control group (46+/-2 vs. 30+/-2 pmol/l). Actually, pancreastatin levels positively correlated with both epinephrine (r = 0.34) and norepinephrine (r = 0.80) levels. CONCLUSIONS: Catecholamine and pancreastatin-like levels were found elevated in gestational diabetic subjects. These counterregulatory hormones may play a role in the insulin resistance syndrome of gestational diabetes.
The Action Profile of Lispro Is Not Blunted by Mixing in the Syringe With NPH Insulin
Authors: Joseph Stonny E , Korzon-Burakowska Anna , Woodworth James R , Evans Mark , Hopkins David , Janes Jonathan M , Amiel Stephanie A
Published: March 2007

OBJECTIVE

To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile.

RESEARCH DESIGN AND METHODS

A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separateoccasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures

RESULTS

Peak plasma insulin levels (2.6 ± 0.8 vs. 2.2 ± 0.6 vs. 1.9 ± 0.6 ng/ml, P = 0.075),total glucose infused (121.5 ± 32.8 vs. 135.0 ± 49.0 vs. 117.3 ± 39.9 mg · kg−1 · min−1 P = 0.53), and maximum glucose infusion rate (GlRmax) (8.3 ± 0.9 vs. 8.0 ± 1.7 vs. 7.1 ± 2.4 mg · kg−1 · min−1 P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 ± 0.3 and 1.2 ± 0.2 vs. 2.0 ± 0.4 h, respectively, P = 0.042). The times until GIRmax were also not different (113.9 ± 41 and 122.0 ± 45 vs. 209.0 ± 51.3 min, , respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 ± 40.5 vs. 292.4 ± 133.3 vs. 399.5 ± 78.3, respectively, P = 0.005).

CONCLUSIONS

The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine typesof insulin before injection to achieve optimal diabetes control.
Mechanism of Impaired Left Ventricular Wall Motion in the Diabetic Heart Without Coronary Artery Disease
Authors: Sakamoto Ken'ya , Yamasaki Yoshimitsu , Shinsuke Nanto , Shimonagata Tsuyoshi , Morozumi Takakazu , Ohara Tomoki , Takano Yuzuru , Nakayama Hiroyuki , Kamado Keiji , Nagata Seiki , Kusuoka Hideo , Nishimura Tsunehiko , Hori Masatsugu
Published: March 2007

OBJECTIVE

To elucidate whether impairment of the myocardial free fatty acid (FFA)metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease

RESEARCH DESIGN AND METHODS

We performed myocardial imaging with 123I-labeled β-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201 thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum

RESULTS

Nine patients with reduced wall motion documented by left ventriculography (LVG) (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 ± 0.2, mean ± SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 ± 0.2, P <0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P <0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients.

CONCLUSIONS

Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes
An Autopsy Case of Troglitazone-Induced Fulminant Hepatitis
Authors: Shibuya Akitaka , Watanabe Masaaki , Fujita Yoshikuni , Saigenji Katsunori , Kuwao Sadahito , Takahashi Hisao , Takeuchi Haruo
Published: March 2007

OBJECTIVE

To study an autopsy case of troglitazone-induced fulminant hepatitis.

CASE REPORT

A 58-year-old man contracted severe hepatitis 2 months after administration of troglitazone for the treatment of type 2 diabetes. Liver damage progressed gradually, even after withdrawal of the agent. Despite intensive therapy, the hepatitis became fulminant and the patient died 8 weeks after the onset of liver damage. Autopsy revealed massive hepatic necrosis and cholestasis with inflammatory cell infiltration. The pathological findings and the positive result of the drug-induced lymphocyte stimulation test for troglitazone indicated that the liver damage was mediated by hypersensitivity to troglitazone.

CONCLUSIONS

One report has attributed troglitazone-induced liver damage in less severe cases to idiosyncratic reactions. However, the present case indicates that troglitazone can induce hypersensitivity resulting in fulminant hepatitis. Careful monitoring of serum liver enzymes during troglitazone therapy is therefore essential.
The Association Between Diabetic Complications and Exercise Capacity in NIDDM Patients
Authors: Estacio Raymond O , Regensteiner Judith G , Wolfel Eugene E , Jeffers Barrett , Dickenson Matthew , Schrier Robert W
Published: March 2007

OBJECTIVE

Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It has been demonstrated previously in NIDDM patients that several risk factors (i.e., obesity, smoking, hypertension, and African-American race) are associated with an impaired exercise capacity. We studied 265 male and 154 female NIDDM patients who underwent graded exercise testing with expired gas analyses to determine the possible influences of diabetic neuropathy, nephropathy, and retinopathy on exercise capacity.

RESEARCH DESIGN AND METHODS

Univariate and multiple linear regression analyses were performed to determine the relationship between diabetic neuropathy, urinary albumin excretion (UAE), and retinopathy with respect to peak oxygen consumption (Vo2). Neuropathy was assessed by neurological symptom and disability scores, autonomic function testing, and quantitative sensory exams involving thermal and vibratory sensation. Three categories of UAE were used: normal albuminuria (<20 μg=min), microalbuminuria (20–200 μg/min), and overt albuminuria (>200 μg/min). Retinopathy was assessed by stereoscopic fundus photographs. Multiple linear regression analyses were then performed controlling for age, sex, length of diagnosed diabetes, duration of hypertension, race and ethnicity, GHb, BMI, and smoking to determine whether there was an independent effect of these diabetic complications on exercise capacity.

RESULTS

Univariate analyses revealed that the presence of diabetic retinopathy (P = 0.03), neuropathy (P = 0.002), microalbuminuria (P = 0.04), and overt albuminuria (P = 0.06) were associated with a lower peak Vo2. Multiple linear regression analyses were performed to determine independent relationships with peak Vo2. The results revealed that increasing retinopathy stage (Parameter estimate [PE] = −0.59 ± 0.3 ml · kg−1 · min−1; P = 0.026) and increasing UAE stage (PE = −0.62 ± 0.3 ml · kg−1 · min−1; P = 0.044) were associated with a decrease in peak Vo2.

CONCLUSIONS

In the present study of NIDDM subjects, a significant independent association was demonstrated between diabetic nephropathy and retinopathy with exercise capacity. These results were obtained controlling for age, sex, length of diagnosed diabetes, hypertension, race, and BMI. Thus the findings in this large NIDDM population without a history of coronary artery disease indicate a potential pathogenic relationship between microvascular disease and exercise capacity.
Long-Term Titrated-Dose α-Glucosidase Inhibition in Non-Insulin-Requiring Hispanic NIDDM Patients
Authors: Johnston Peter S , Feig Peter U , Coniff Robert F , Krol Alice , Davidson Jaime A , Haffner Steven M
Published: March 2007

OBJECTIVE

To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients.

RESEARCH DESIGN AND METHODS

A 1-year double-blind randomized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150, 200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability. Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of tabulation of adverse events and intercurrent illnesses, and of periodic laboratory determinations.

RESULTS

Reductions from baseline in HbA1c levels at the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in the miglitol group than in the placebo group. HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63, 0.73, and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120-min postprandial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits. There was little difference between treatments for changes in fasting insulin or lipid levels. Miglitol-associated reductions versus placebo in fasting plasma glucose (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly statistically significant. These efficacy results were not notably different between the 6-month endpoint, at which time the mean miglitol dose was 100 mg t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d. Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea (or soft stools). The incidence of these gastrointestinal adverse events appeared to be dose dependent.

CONCLUSIONS

Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d. produced statistically and clinically significant reductions of HbA1c, primarily associated with reduction of glucose and insulin levels in the postprandial period, which were sustained over a year of treatment. Adverse events related to the drug's mechanism of action were common, but generally well tolerated. Doses above 100 mg t.i.d. were not associated with notably enhanced efficacy in most patients.
Leptinemia Is Not a Risk Factor for Ischemic Heart Disease in Men: Prospective results from the Quebec Cardiovascular Study
Authors: Couillard Charles , Lamarche Benoît , Mauriège Pascale , Cantin Bernard , Dagenais Gilles R , Moorjani Sital , Lupien Paul-J , Després Jean-Pierre
Published: March 2007

OBJECTIVE

To investigate the possibility that leptin levels may be predictive of the risk of ischemic heart disease (IHD) through the relationship of leptin to body fat.

RESEARCH DESIGN AND METHODS

The Quebec Cardiovascular Study cohort consisted of 2,103 French-Canadian men without IHD in 1985 who were followed until 1990, by which time 114 had experienced an IHD event. These 114 men were then individually matched for age, BM1, cigarette smoking, and alcohol intake with 114 subjects who were free of IHD at follow-up. After exclusion of diabetic patients and those in whom leptin levels could not be measured, we were able to compare the initial metabolic profiles of 86 men in the IHD group and of 95 control subjects.

RESULTS

Plasma leptin concentrations were positively correlated with BMI (r = 0.67, P < 0.0001) and with fasting insulin concentrations (r = 0.46, P < 0.0001) in the overall sample. These significant associations were also observed when men with IHD and the control subjects were examined separately (control subjects: r = 0.68 for BMI and r = 0.45 for insulin; IHD subjects: r = 0.65 for BMI and r = 0.50 for insulin). With the exception of plasma triglyceride (r = 0.25, P < 0.001), no significant association was found between leptin and plasma lipoprotein and lipid concentrations. Furthermore, plasma insulin remained significantly associated with leptin levels even after adjustment for BMI (r = 0.22, P < 0.005). There was no difference in baseline leptin levels among men who developed IHD versus men who remained IHD-free during the 5-year follow-up (5.56 ± 3.12 vs. 5.36 ± 2.90 ng/ml, respectively). Thus, although significantly correlated with the BMI and fasting insulin levels, plasma leptin concentration was not a significant predictor of the 5-year incidence of IHD. This lack of a relationship to IHD was noted when leptin levels were analyzed as tertiles and when leptin concentration was analyzed as a continuous variable.

CONCLUSIONS

These prospective results suggest that leptinemia, despite being a strong correlate of obesity, does not appear to be an independent risk factor for the development of IHD in men.
Personal and Family Factors Associated With Quality of Life in Adolescents With Diabetes
Authors: Grey Margaret , Boland Elizabeth A , Yu Chang , Sullivan-Bolyai Susan , Tamborlane William V
Published: March 2007

OBJECTIVE

Quality of life is an important criterion for assessing outcomes of treatment in chronic illness related to psychosocial well-being. The purpose of this study was to evaluate the factors that influence quality of life in adolescents with IDDM.

RESEARCH DESIGN AND METHODS

Self-reports were obtained from 52 adolescents (age 13-20 years, mean 16.1 ± 1.9 [mean ± SD], diabetes duration 8.2 ± 3.4 years, 49% female) using the following scales: Diabetes Quality of Life for Youths, Children's Depression Inventory, Issues in Coping with Diabetes, Diabetes Family Behavior Scale, Family Adaptability and Cohesion, Self-Efficacy for Diabetes, and the Adolescent Coping Orientation. Metabolic control was measured by HbA1c.

RESULTS

Teenagers whose diabetes had the greater impact (R2 = 0.48) and were less satisfied (R2 = 0.45) felt that management was more difficult (r = 0.56) and that diabetes was more upsetting (r = 0.63). They also used fewer rebellion strategies for coping (r = −0.44), had lower diabetes self-efficacy (r = −0.36), and had more depressive symptoms (r = 0.61). Higher impact was also associated with higher family warmth and caring (r = −0.54) and lower family adaptability (r = −0.42). Teenagers who were more worried (R2 = 0.37) about their diabetes felt that management was more difficult (r = 0.40) and that diabetes was more upsetting (r = 0.58), and they used less rebellion (r = −0.49) and more ventilation (r = 0.42) to cope, had lower diabetes (r = −0.40) and medical (r = −0.30) self-efficacy, were more depressed (r = 0.55), and their families were less warm and caring (r = −0.33). HbA1c levels were not associated with quality of life or any other psychosocial factors except in teenagers who perceived their families as providing more guidance and control. These teenagers had lower HbA1c values than those whose families were less involved.

CONCLUSIONS

Even teenagers who are successfully achieving HbA1c goals of therapy may perceive diabetes as having a negative impact on their lives, be depressed, and find diabetes difficult to manage. Diabetes treatment teams need to pay equal attention to the psychosocial needs to the quiet, nonrebellious teen with well-controlled diabetes from a supportive family as they do to the rebellious adolescent with poorly controlled diabetes.
Identification and Treatment of Cystic Fibrosis-Related Diabetes: A survey of current medical practice in the U.S
Authors: Allen Holley F , Gay Elizabeth C , Klingensmith Georgeanna J , Hamman Richard F
Published: March 2007

OBJECTIVE

To describe physicians' attitudes and practices in screening for and treating abnormalities in glucose homeostasis in cystic fibrosis (CF) patients and to test the hypotheses that guidelines for screening for CF-related diabetes (CFRD) are not followed at most centers and that screening and treatment vary by the care provider's background.

RESEARCH DESIGN AND METHODS

This cross-sectional survey included three groups of physicians: 1) 593 members of the Lawson Wilkins Pediatric Endocrine Society (LWPES), 2) 462 members of the pediatric assembly of the American Thoracic Society (ATS), and 3) 194 directors of cystic fibrosis centers (CFD). A mailed questionnaire was used for the survey.

RESULTS

The overall response rate was 67%. Of these, 224 LWPES, 143 ATS, and 135 CFD physicians reported actively seeing CF patients. About two-thirds of CF physicians (ATS and CFD) reported routine screening for impaired glucose tolerance (IGT) in asymptomatic CF patients; a random glucose is most often used (60%), followed by HbA1c (50%), urine glucose (44%), fasting glucose (21%), and oral glucose tolerance test (2%). Only 40% of LWPES physicians reported intervening for stress-induced hyperglycemia, but 61% reported use of insulin for persistent IGT. Management of CFRD was similar for all groups; most physicians used insulin (91%). LWPES recommended more intensive glucose testing and nutritional guidelines than did ATS/CFD (P < 0.0001). LWPES reported less concern about risks of diabetes complications (P < 0.0001) and the importance of minimizing burdensome interventions (P < 0.01). All groups considered weight management a top priority.

CONCLUSIONS

Screening for IGT is not routinely done in CF patients and screening tests vary. Greater agreement exists on methods of treating patients with persistent IGT or CFRD, although goals and aggressiveness of treatment vary with the provider's background. A consensus conference is recommended.
Prevalences of Type 2 Diabetes, the Insulin Resistance Syndrome, and Coronary Heart Disease in an Elderly, Biethnic Population
Authors: Lindeman Robert D , Romero Linda J , Hundley Rosalina , Allen Andrew S , Liang Hwa Chi , Baumgartner Richard N , Koehler Kathleen M , Schade David S , Garry Philip J
Published: March 2007

OBJECTIVE

To compare the prevalences of type 2 diabetes, the various cardiovascular risk factors encompassing the insulin resistance syndrome (IRS), and coronary heart disease (CHD) in elderly Hispanics compared with non-Hispanic whites.

RESEARCH DESIGN AND METHODS

Elderly Hispanics (n = 414) and non-Hispanic whites (n = 469), randomly selected from the Medicare rolls of Bernalillo County (Albuquerque, NM; age ≥ 65 years), underwent a home interview followed by an interview/examination by a nurse-practitioner, nurse, and nutritionist that included an evaluation of glucose tolerance. Prevalences of total and central obesity, dyslipidemia, hypertension, and microalbuminuria also were determined. History of myocardial infarction, recent angina, and/or coronary bypass graft, and electrocardiograms (ECGs) were used to document CHD.

RESULTS

Elderly Hispanics had twice the prevalence of type 2 diabetes compared with non-Hispanic whites, but the prevalence of impaired glucose tolerance was not increased in Hispanics. Mean serum fasting and 2-h post-glucola insulin concentrations, fasting insulin resistance indexes, and HbA1c were higher in Hispanics. Hispanics were shorter, weighed less, and had more total body and central obesity. The higher prevalences of dyslipidemia in Hispanics could be explained by a higher prevalence of diabetes. The prevalences of hypertension and CHD were not different for the two ethnic groups.

CONCLUSIONS

Elderly Hispanics had twice the prevalence of diabetes and higher prevalences of cardiovascular risk factors associated with IRS. Prevalences of hypertension and CHD were similar in the two ethnic groups.
Glucose Metabolism, Lipid Metabolism, and Cardiovascular Risk Factors in Adult Turner's Syndrome: The impact of sex hormone replacement
Authors: Gravholt Claus Højbjerg , Naeraa Rune Weis , Nyholm Birgit , Gerdes Lars Ulrik , Christiansen Erik , Schmitz Ole , Christiansen Jens Sandahl
Published: March 2007

OBJECTIVE

To examine glucose metabolism, blood pressure, physical fitness, and lipid metabolism in adult untreated women with Turner's syndrome compared with a group of normal women and to examine the effects of female sex hormone substitution on these factors.

RESEARCH DESIGN AND METHODS

A total of 26 patients with Turner's syndrome were examined before and during sex hormone replacement with 17β-estradiol and norethisterone, and an age-matched control group (n = 24) was examined once. A frequently sampled intravenous glucose tolerance test was applied with minimal model assessment. We also performed an oral glucose tolerance test, measurement of 24-h ambulatory blood pressure, and assessment of physical fitness and lipid metabolism.

RESULTS

Insulin sensitivity (SI) and glucose effectiveness (SG) were similar in Turner's syndrome patients and control subjects, whereas the acute insulin response (P = 0.03) was lower in Turner's syndrome patients, and no change was seen during sex hormone treatment. Abnormal glucose tolerance was found in 50% of Turner's syndrome patients before and 78% during treatment with sex hormones. Fat-free mass (FFM; P = 0.0005) and physical fitness (P = 0.002) were lower in Turner=s syndrome subjects compared with control subjects. During treatment, an increase in FFM (P = 0.001) and physical fitness (P = 0.02) was seen in Turner's syndrome patients. Blood pressure was increased in Turner's syndrome, and a decrease was seen in diastolic blood pressure during treatment with sex hormones.

CONCLUSIONS

Turner's syndrome is associated with glucose intolerance, diminished first-phase insulin response, elevated blood pressure, reduced FFM, and physical fitness. Sex hormone administration causes a deterioration in glucose tolerance, increases FFM and physical fitness, and has beneficial effects on blood pressure. The deleterious effect on glucose tolerance may be mediated by norethisterone, a gestagen known to have androgenic effects.
Comparison of the Seasonal Pattern in the Clinical Onset of IDDM in Finland and Sardinia
Authors: Karvonen Marjatta , Jäntti Virva , Muntoni Sandro , Stabilini Marco , Stabilini Liliana , Muntoni Sergio , Tuomilehto Jaakko
Published: March 2007

OBJECTIVE

To examine the seasonal pattern for the clinical onset of IDDM in Finland and Sardinia, two areas where the incidence of IDDM is the highest in the world, and to determine the effect of climate and temperature on the clinical onset of IDDM.

RESEARCH DESIGN AND METHODS

Analysis of seasonality for the diagnosis of IDDM was based on 1,405 cases in Finland and 425 cases in Sardinia diagnosed at ≤14 years of age from 1989 to 1992. The average annual incidence of IDDM was 36.4/100,000 in Finland and 34.4/100,000 in Sardinia. Seasonal patterns were estimated presenting the data as short Fourier series up to three harmonics together with a possible linear trend. Likelihood ratio tests and Akaike's information criterion were used to determine the number of harmonics necessary to model the seasonal pattern. Seasonal patterns in both countries were compared between sexes and between the three 5-year age-groups, each controlling for the other's effect.

RESULTS

In both countries, a significant seasonal pattern during a calendar year was found for the sexes combined and for two age-groups (0–9 and 10–14 years). In Sardinia, two distinct cycles were found in the younger age-group, with a decreased incidence during May through August and an increased incidence during the autumn months. Two cycles were apparent in the older age-group, with the nadir occurring during June through September. In Finland, one cycle was found in the younger age-group, with a decreased incidence in June. In the older age-group, there were two distinct cycles, with a decreased incidence in June and in the September through December period.

CONCLUSIONS

Differences between Finland and Sardinia in the seasonal pattern for the incidence of newly diagnosed IDDM cannot be explained by differences in climate, temperature, a longer warm period in Sardinia, or other climatic phenomena. The results do not provide evidence in favor of a specific viral etiology of IDDM. It may be suggested that there are triggering events at certain times, but they are likely to be unspecinc. Nevertheless, why the incidence of IDDM in these two populations is equally high despite differences in climate, environment, and genetic background remains an unsolved question.
Glucokinase Gene Islet Promoter Region Variant (G→A) at Nucleotide −30 Is Not Associated With Reduced Insulin Secretion in Finns
Authors: Rissanen Johanna , Saarinen Laura , Heikkinen Sami , Kekäläinen Päivi , Mykkänen Leena , Kuusisto Johanna , Deeb Samir S , Laakso Markku
Published: March 2007

OBJECTIVE

To investigate the effect of the islet promoter region variant (G→A) at nucleotide −30 of the glucokinase (GCK) gene on insulin levels in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM.

RESEARCH DESIGN AND METHODS

The study population included 294 subjects with NGT, 83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests (OGTTs) were performed in all subjects, and intravenous glucose tolerance tests (IVGTTs) were performed in subjects with NGT. The islet promoter region of the GCK gene was amplified with polymerase chain reaction and screened for the variant (−30) using single-strand conformation polymorphism analysis.

RESULTS

The islet promoter variant (−30) of the GCK gene was found in 17% of subjects with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not differ between subjects with and without this variant in any of the three groups. Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects with NGT, did not associate with presence of the islet promoter region variant (−30) of the GCK gene.

CONCLUSIONS

These results indicate that the variant (−30) of the islet promoter region of the GCK gene does not have a significant effect on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.
Insufficient Glycemic Control Increases Nuclear Factor-κB Binding Activity in Peripheral Blood Mononuclear Cells Isolated From Patients With Type 1 Diabetes
Authors: Hofmann Marion A , Schiekofer Stephan , Kanitz Michael , Klevesath Martina S , Joswig Martina , Lee Vong , Morcos Michael , Tritschler Hans , Ziegler Reinhard , Wahl Peter , Bierhaus Angelika , Nawroth Peter P
Published: March 2007

OBJECTIVE

The redox-sensitive transcription factor nuclear factor-kB (NF-kB) is believed to contribute to late diabetic complications. It is unknown whether NF-kB is influenced by glycemic control.

RESEARCH DESIGN AND METHODS

To determine whether NF-kB is activated in patients with insufficient glycemic control (HbA1c > 10%), we developed a tissue culture-independent electrophoretic mobility shift assay (EMSA)-based semiquantitative detection system that allowed us to determine NF-kB activation in ex vivo-isolated peripheral blood mononuclear cells (PBMCs). We included 43 patients with type 1 diabetes in this cross-sectional study. 10 of those received the antioxidant thioctic acid (600 mg/day p.o.) for 2 weeks.

RESULTS

Monocytes of patients with HbA1c levels > 10% demonstrated significantly higher NF-kB binding activity in an EMSA and a stronger NF-kB staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6–8%. The increase in NF-kB activation correlated with an increase in plasmatic markers of lipid peroxidation. Treatment with the antioxidant thioctic acid decreased NF-kB binding activity.

CONCLUSIONS

Hyperglycemia induces activation of the transcription factor NF-kB in ex vivo-isolated PBMCs of patients with type 1 diabetes. NF-kB activation is at least partially dependent on oxidative stress, since the antioxidant thioctic acid significantly lowered the extent of NF-kB binding activity.