bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Empowerment: Results of a randomized controlled trial
Authors: Anderson Robert M , Funnell Martha M , Butler Patricia M , Arnold Marilynn S , Fitzgerald James T , Feste Catherine C
Published: March 2007

OBJECTIVE

The purpose of this study was to determine if participation in a patient empowerment program would result in improved psychosocial self-efficacy and attitudes toward diabetes, as well as a reduction in blood glucose levels.

RESEARCH DESIGN AND METHODS

This study was conducted as a randomized, wait-listed control group trial. The intervention group received a six-session (one session per week) patient empowerment education program; the control group was assigned to a wait-list. At the end of 6 weeks, the control group completed the six-session empowerment program. Six weeks after the program, both groups provided follow-up data.

RESULTS

The intervention group showed gains over the control group on four of the eight self-efficacy subscales and two of the five diabetes attitude subscales. Also, the intervention group showed a significant reduction in glycated hemoglobin levels. Within groups, analysis of data from all program participants showed sustained improvements in all of the self-efficacy areas and two of the five diabetes attitude subscales and a modest improvement in blood glucose levels.

CONCLUSIONS

This study indicated that patient empowerment is an effective approach to developing educational interventions for addressing the psychosocial aspects of living with diabetes. Furthermore, patient empowerment is conducive to improving blood glucose control. In an ideal setting, patient education would address equally blood glucose management and the psychosocial challenges of living with diabetes.
The Prevalence and Severity of Microvascular Complications in Pancreatic Diabetes and IDDM
Authors: Levitt Naomi S , Adams Ganief , Salmon John , Marks I N Solly , Musson Gregory , Swanepoel Charles , Levy Margaret , Byrne Michael J
Published: March 2007

OBJECTIVE

To investigate and compare the prevalence, associations, and severity of retinopathy and nephropathy in patients with pancreatic diabetes (PD) and insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS

Thirty patients with PD due to alcohol-induced chronic pancreatitis were matched for age, sex, and duration of diabetes with 30 patients with IDDM. Retinopathy was assessed by fluorescein angiography using the Wisconsin classification. Renal function was assessed by albumin excretion rates (AERs) in at least two timed overnight urine collections and glomerular filtration rates (GFRs) by single injection of 51Cr-EDTA. Microalbuminuria was defined as AER 20–200 μg/min and nephropathy as AER > 200 μg/min.

RESULTS

Retinopathy was found in 33% of patients with PD and in 40% with IDDM. The spectrum of disease was similar in the two groups. The geometric mean of AER was 15 μg/min (range 1–1,541) in the PD group and 24 μg/min (2–2,288) in the IDDM group. Nephropathy was found in 7 PD and in 5 IDDM patients, and a reduced GFR was present in 8 (26%) and 4 (13%) of the two groups, respectively. Microalbuminuria occurred in 9 (33%) and hyperfiltration in 3 (10%) in each group. These differences were insignificant. Retinopathy correlated with AER in both groups. Retinopathy and AER correlated with duration of diabetes in the IDDM but not in the PD group.

CONCLUSIONS

Microvascular complications are equally common and severe in PD and IDDM, and improved glycemic control should be the goal in both.
Noninvasive Detection of Functional Alterations of the Arterial Wall in IDDM Patients With and Without Microalbuminuria
Authors: Zenere Beatrice M , Arcaro Guido , Saggiani Francesca , Rossi Luca , Muggeo Michele , Lechi Alessandro
Published: March 2007

OBJECTIVE

To test endothelial function in a group of 10 normoalbuminuric and eight microalbuminuric insulin-dependent diabetes mellitus patients (ages 28 ± 3 [mean ± SE] and 28 ± 1 years, respectively), in comparison with 16 control subjects (age 35 ± 2 years, normal subjects vs. diabetic subjects P = NS), to identify prestructural abnormalities of the arterial wall. An early stage of vascular involvement seems in fact to be characterized by functional alterations of endothelial control on vascular tone and wall interaction with circulating cells. Furthermore, many recent studies suggest the importance of microalbuminuria as an early marker not only of nephropathy but also of retinopathy and macroangiopathy.

RESEARCH DESIGN AND METHODS

Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation (induced by glyceryl trinitrate administration) were evaluated in the right common femoral artery by echo-Doppler ultrasound. Arterial wall distensibility was evaluated at the common femoral artery by an echo-tracking system.

RESULTS

In spite of a comparable increase in flow velocity, endothelium-mediated vasodilation was significantly reduced in diabetic subjects, particularly in microalbuminuric patients. Endothelium-independent vasodilation was also significantly impaired in diabetic subjects, particularly in microalbuminuric subjects; whereas arterial wall distensibility, an index of the viscoelastic properties of the wall, was similar in the three groups.

CONCLUSIONS

These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.
Absorption of Rapid-Acting Insulin in Obese and Nonobese NIDDM Patients
Authors: Clauson Per G , Linde Birgitta
Published: March 2007

OBJECTIVE

To study the absorption rate of rapid-acting insulin from subcutaneous injection sites in nonobese and obese non-insulin-dependent diabetes mellitus (NIDDM) patients.

RESEARCH DESIGN AND METHODS

Ten nonobese and 10 obese NIDDM patients (body mass indexes 24.1 ± 0.4 and 31.4 ± 0.8 kg/m2, respectively) received four subcutaneous injections of 125I-labeled rapid-acting insulin (Actrapid Human, 5 U): three in the abdominal wall above, lateral to, and below the umbilicus; and one in the thigh. The depth of the subcutaneous fat layer was measured using ultrasound techniques. The residual radioactivity was monitored externally for 270 min.

RESULTS

The disappearance half-life of 125I-insulin was between 4 and 6 h from all injection sites, with the exception of the upper abdominal area in the nonobese subjects, where it measured ∼ 3 h. The residual radioactivity did not differ between nonobese and obese patients measured from any of the sites. In the nonobese group, the most rapid absorption of 125I-insulin was found from the upper abdominal area and the slowest from the thigh. In the obese group, the absorption rates did not differ between sites. No correlation was found between the depth of the fat layer and the residual radioactivity when measured at any site.

CONCLUSIONS

Our results indicate that the absorption of rapid-acting insulin is markedly slow in both obese and nonobese NIDDM patients compared with IDDM patients and healthy subjects studied previously. In the nonobese group, the most rapid absorption of 125I-insulin is obtained after injection into the upper abdominal area. Inter- and intraregional differences are small in the obese patients. Consequently the choice of injection site is of little importance in this group.
Release of Platelet Plasminogen Activator Inhibitor 1 in Whole Blood Is Increased in Patients With Type II Diabetes
Authors: Jokl Rudolf , Klein Richard L , Lopes-Virella Maria F , Colwell John A
Published: March 2007

OBJECTIVE

To compare platelet plasminogen activator inhibitor 1 (PAI-1) release in type II diabetic patients and healthy control subjects.

RESEARCH DESIGN AND METHODS

We studied a group of 27 diabetic patients and a group of 16 nondiabetic control subjects. Whole-blood platelet aggregation, defined as a decrease in platelet count during shaking (180 rpm) of blood samples at 37°C, and plasma PAI-1 antigen concentrations were measured in parallel at time 0, 7.5, 15, 30, 60, 120, and 180 min.

RESULTS

Platelet aggregation did not differ significantly between the two groups at any time period. However, the increase in plasma PAI-1 antigen concentration over basal levels at time 0 was higher for the group of diabetic patients when compared with their matched control subjects. The increment of PAI-1 antigen was 61.8 ± 29.4 vs. 35.9 ± 13.4 ng/ml (P < 0.005, means ± SD) after 180 min for the diabetic and control subjects, respectively. Platelet PAI-1 release was correlated to very-low-density lipoprotein cholesterol and triglyceride plasma levels, but not to HbA1c levels.

CONCLUSIONS

Platelets of patients with type II diabetes release significantly more PAI-1 than platelets of healthy subjects at the same level of platelet aggregation. This may contribute to enhanced thrombosis in diabetes.
Lipoic Acid Improves Nerve Blood Flow, Reduces Oxidative Stress, and Improves Distal Nerve Conduction in Experimental Diabetic Neuropathy
Authors: Nagamatsu Masaaki , Nickander Kim K , Schmelzer James D , Raya Angel , Wittrock Debra A , Tritschler Hans , Low Phillip A
Published: March 2007

OBJECTIVE

To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy.

RESEARCH DESIGN AND METHODS

We used the model of streptozotocin-induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes.

RESULTS

NBF in SDN was reduced by 50% LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was improved in a dose-dependent manner in LA-supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA.

CONCLUSIONS

These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of human diabetic neuropathy.
Phospholipid and Glutamic Acid Decarboxylase Autoantibodies in Diabetic Neuropathy
Authors: Vinik Aaron I , Leichter Steven B , Pittenger Gary L , Stansberry Kevin B , Holland Marie T , Powers Alvin C , Suwanwalaikorn Sompongse
Published: March 2007

OBJECTIVE

To determine the prevalence and significance of phospholipid autoantibodies (PLAs) and glutamic acid decarboxylase (GAD) autoantibodies in the circulation of normal patients and diabetic patients with and without neuropathy.

RESEARCH DESIGN AND METHODS

We measured PLAs in a total of 78 patients (a diabetic group with somatic or autonomic neuropathy [n = 40] another group without neuropathy [n = 38]), and GAD autoantibodies in a subset of 22 patients.

RESULTS

PLAs are found in 2% of the general population. We found PLAs in 32% of the diabetic population without neuropathy, in 88% of those with neuropathy, in 55% of those with retinopathy, and in 25% of those with established nephropathy. The frequencies of immunoglobulins in the neuropathic group were: IgG = 78%, IgM = 33%, and IgA = 23%. There was no correlation between PLAs and microalbuminuria, macrovascular disease, fibrinogen, duration of diabetes, or neuropathy, but there was a strong correlation with total neuropathy score. Sera with high PLA IgG titers bound to the surface of neuroblastoma cells and inhibited cell growth. Antibodies to GAD65 were present in 32% and to GAD67 in 0% of patients. No titers of GAD65, GAD67, or the GAD65 ratio were associated with the degree of neuropathy of the presence of PLAs.

CONCLUSIONS

PLAs occur frequently in the sera of patients with diabetes and correlate with the extent of neuropathy, suggesting a role for PLAs in the etiology thereof. The measurement of PLAs may constitute a marker for ongoing damage to nerves.
Renal, Metabolic, and Hormonal Responses to Proteins of Different Origin in Normotensive, Nonproteinuric Type I Diabetic Patients
Authors: Kontessis Panayotis A , Bossinakou Irini , Sarika Leda , Iliopoulou Elsa , Papantoniou Antonis , Trevisan Roberto , Roussi Demetra , Stipsanelli Katherine , Grigorakis Stelios , Souvatzoglou Athanasios
Published: March 2007

OBJECTIVE

Whether the differences in renal function found in vegetarian compared with omnivorous subjects are related to quantity or quality of the protein is unknown. We have studied the renal function of nine normotensive, nonproteinuric type I diabetic patients who were fed in random order for 4 weeks either an animal protein diet (APD) (protein intake 1.1 g · kg−1 · day−1) or a vegetable protein diet VPD (protein intake 0.95 g · kg−1 · day−1). The two diets were isocaloric.

RESEARCH DESIGN AND METHODS

In a crossover study, we measured glomerular filtration rate (GFR) (inulin clearance), renal plasma flow (RPF) (p-aminohippurate clearance), plasma amino acids, growth hormone, glucagon, insulin-like growth factor I-(IGF-I), and microalbuminuria.

RESULTS

GFR and RPF were lower with the VPD than with the APD (89.9 ± 4.1 vs. 105.6 ± 5.1 ml · min−1 · 1.73 m−2, P < 0.05, and 425.7 ± 22.2 vs. 477.8 ± 32.2 ml · min−1 1.73m−2, P < 0.05, respectively). Renal vascular resistance (RVR) was higher with the VPD than with the APD (101 ± 25 vs. 91 ± 10 mmHg · min−1 · ml−1, P < 0.05). Filtration fraction (FF) remained unchanged after either diet. Fractional clearance of albumin fell with the VPD to 2.0 ± 0.65 from 3.4 ± 1.15 × 10−6 (P < 0.05). At the end of the APD and VPD, the plasma levels of growth hormone and glucagon did not differ significantly. Plasma levels of IGF-I were higher with the APD than with the VPD (1.1 ± 0.6 vs. 0.9 ± 0.13 U/ml, P < 0.05). Plasma concentrations of valine and lysine were significantly higher with the APD than with the VPD (234.6 ± 30.3 vs. 164.5 ± 25.4 mmol/1, P < 0.05, and 565 ± 45.1 vs. 430 ± 56.1 mmol/l, P < 0.05, respectively), whereas plasma valine was strongly correlated to the GFR (r = 0.832, P < 0.01). No differences were found in other amino acids.

CONCLUSIONS

A VPD has significantly different renal effects from an APD equal in protein intake in normotensive type I diabetic patients. This could be explained partly by differences in plasma concentrations of amino acids and IGF-I.
Prevalence Estimates of Diabetes and of Other Cardiovascular Risk Factors in the Two Largest Algonquin Communities of Quebec
Authors: Delisle Hélène F , Rivard Michèle , Ekoé Jean-Marie
Published: March 2007

OBJECTIVE

To compare the prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in the two largest Algonquin communities of Quebec (Canada) with that of other native groups and to describe the different patterns of NIDDM and other cardiovascular risk markers in these communities (River Desert [RD] and Lac Simon [LS]).

RESEARCH DESIGN AND METHODS

The population-based study targeted all residents aged 15 years and older. In the age-group considered here (30-64 years), there were 480 eligible subjects and 299 participants (50.8% in RD and 86.9% in LS). All except those with confirmed diabetes underwent an oral glucose tolerance test. Serum triglyceride and lipoprotein cholesterol levels, blood pressure, body mass index (BMI), and waist-to-hip ratio (WHR) were measured.

RESULTS

The age-standardized (world population) prevalence of NIDDM in women was twice as high in LS as in RD (48.6% vs. 23.9%). In men, it was 23.9% in LS and 16.3% in RD. Upper-body obesity followed the same pattern. In contrast, high-risk serum low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels were significantly more prevalent in RD than in LS, particularly among men. The rate of high blood pressure was twice as high in men as in women, with little community differences. When we controlled for age, sex, diabetic, and obesity status, mean fasting serum glucose remained significantly higher triglycerides and LDL cholesterol lower in LS than in RD. There was also an independent community effect on WHR but no on BMI.

CONCLUSIONS

The prevalence of NIDDM in LS women reaches the rate observed in Pima Indian women. The observed differences between two Algonquin communities suggest a highly heterogeneous pattern of NIDDM and cardiovascular disease risk factors in Amerindian populations, even within a given tribe and a limited geographic area.
Lack of Long-Term Diabetic Complications in Spite of Poor Glycemic Control in Twins With Pure Gonadal Dysgenesis
Authors: Bell David S H
Published: March 2007

BACKGROUND

The prepubertal years have little effect on the chronic complications of diabetes. Animal studies have shown castration prevents diabetic complications. No previous data on untreated agonadal human diabetic subjects is available.

CASE HISTORY

Clinical study of untreated agonadal twins with insulin-dependent diabetes for presence of chronic complications of diabetes. In spite of the twins' poor glycemic control, no evidence of the chronic complications of diabetes was found.

CONCLUSIONS

The absence of gonadal sex steroids in the diabetic patient may have a protective effect against the development of the chronic complications of diabetes.
Erythrocyte Sodium-Lithium Countertransport Activity in Non-Nephropathic Diabetic Twins
Authors: Hardman Timothy C , Dubrey Simon W , Leslie R David G , Lant Ariel F
Published: March 2007

OBJECTIVE

It has proved difficult to separate the role of the diabetic state as distinct from its complications in causing the elevation in erythrocyte sodium-lithium (Na-Li) countertransport activity that has been observed in diabetes. The present study sought to isolate the impact of diabetes on the countertransporter by studying groups of non-nephropathic identical-twin pairs both discordant and concordant for diabetes.

RESEARCH DESIGN AND METHODS

We studied erythrocyte Na-Li countertransport activity in 49 identical-twin pairs who were discordant for IDDM and 26 identical twin pairs who were concordant for IDDM. Similar numbers of healthy control subjects, matched with the nondiabetic twins from the discordant pairs in respect to sex, BMI, and age were also studied.

RESULTS

The clinical and laboratory characteristics of both sets of twins were very similar to those of the control subjects with the exception that whole-blood glucose and glycated hemoglobin concentrations were higher in diabetic twins, whether from discordant or concordant pairs (P < 0.001), and that systolic blood pressure (P < 0.05) and serum HDL cholesterol (P < 0.05) were higher in the discordant diabetic twins than in their nondiabetic co-twins. Median (95% CI) Na-Li countertransport activities (in millimoles of lithium released from 1 liter of erythrocytes per hour) in the nondiabetic discordant twin [0.237 (0.192–0.284)], the diabetic discordant twin [0.284 (0.254–0.326)], and the concordant twin [0.262 (0.207–0.358)] groups were similar to each other and higher than in the control subjects [0.172 (0.138–0.203)]. Countertransport activities in the discordant diabetic twins correlated significantly with their nondiabetic co-twins (r = 0.34; P = 0.015; n = 49), as did those between the concordant diabetic twin pairs (r = 0.68; P < 0.005; n = 26); activity levels were not related to either disease duration or blood glucose control.

CONCLUSIONS

An elevation in Na-Li countertransport activity has been noted in non-nephropathic normotensive twin pairs both discordant and concordant for IDDM. The potential genetic contribution to the altered behavior of the countertransporter was similar in both types of twins studied, and individual Na-Li countertransport activities were not significantly related to either duration of diabetes or metabolic control.
LDL Apheresis Reduces the Susceptibility of LDL to in Vitro oxidation in a Diabetic Patient With Hemodialysis Treatment
Authors: Inoue Ikuo , Takahashi Keiichi , Kikuchi Chitose , Katayama Shigehiro
Published: March 2007

OBJECTIVE

We studied whether LDL apheresis would alter the susceptibility of LDL to in vitro oxidative modification induced by copper ion in a diabetic patient undergoing hemodialysis treatment.

RESEARCH DESIGN AND METHODS

Isolated LDL was dialyzed against phosphate-buffered saline and resuspended at a concentration of 0.3 mg cholesterol mass/ml buffer LDL oxidation was then initiated by addition of 1.66 μmol/l CuSO4, and the formation of conjugated dienes was continuously monitored spectrophotometrically at 234 nm.

RESULTS

The duration of the lag phase of LDL obtained after LDL apheresis was markedly longer than that of LDL obtained before LDL apheresis. The propagation rate and the maximum conjugated diene formation of LDL oxidation were not changed after LDL apheresis.

CONCLUSIONS

A LDL subfraction that was susceptible to oxidation was removed by LDL apheresis, resulting in reduction of susceptibility of LDL to in vitro oxidation remaining in plasma. LDL apheresis may be of clinical importance for preventing atherosclerotic disease in diabetic patients undergoing hemodialysis.
Hypertriglyceridemia Enhances Monocyte Binding to Endothelial Cells in NIDDM
Authors: Hoogerbrugge Nicoline , Verkerk Anton , Jacobs Marloes L , Postema Pieter TE , Jongkind Johan F
Published: March 2007

OBJECTIVE

The mechanisms by which diabetes leads to rapidly progressive atherosclerosis are not fully understood. Adherence of monocytes to the arterial wall is an early event in the development of atherosclerotic lesions.

RESEARCH DESIGN AND METHODS

The binding of freshly isolated monocytes from patients with NIDDM, IDDM, and healthy control subjects to a monolayer of endothelial cells obtained from human umbilical vein was investigated.

RESULTS

Endothelial adherence of monocytes from normolipidemic patients with IDDM (15.8 ± 4.5%) or NIDDM (16.9 ± 4.6%) was comparable to that of monocytes from a control population (15.3 ± 3.5%). In patients with NIDDM with a serum triglyceride concentration > 2.5 mmol/l, the percentage of cells that adhere to endothelial cells in vitro was significantly increased (23.3 ± 3.1%). Glycemic control did not correlate with monocyte adherence. The presence of symptomatic atherosclerotic disease, age, or sex was not associated with a change in monocyte binding in vitro.

CONCLUSIONS

The results suggest that in NIDDM hypertriglyceridemia should be treated to reduce the high risk for atherosclerosis.
The Effect of Acarbose on Insulin Sensitivity in Subjects With Impaired Glucose Tolerance
Authors: Chiasson Jean-Louis , Josse Robert G , Leiter Lawrence A , Mihic Marko , Nathan David M , Palmason Carol , Cohen Robert M , Wolever Thomas MS
Published: March 2007

OBJECTIVE

To study the effect of acarbose, an α-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS

Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test.

RESULTS

While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 ± 0.5 vs. 3.76 ± 0.6 mmol·h−1 · l−1, P = NS; 1,488 ± 229 vs. 1,609 ± 253 pmol · h−1 · l−1, P = NS), acarbose resulted in a significant reduction for both glucose (1.44 ± 0.3 vs. 4.45 ± 0.9 mmol · h−1 · l−1, P = 0.002) and insulin (626.7 ± 104.3 vs. 1,338.3 ± 220.5 pmol · h−1 · l−1, P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 ± 2.1 mmol · h−1 · l−1 and 7.5 ± 0.7 nmol · h−1 · l−1) was significantly greater than that on placebo (4.0 ± 1.6 mmol · h−1 · l−1 and 0.8 ± 0.4 nmol · h−1 · l−1) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 ± 0.4 vs. 13.8 ± 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 ± 1.4 vs. 13.1 ± 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02).

CONCLUSIONS

It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM.
The Antidiabetogenic Effect of GLP-1 Is Maintained During a 7-Day Treatment Period and Improves Diabetic Dyslipoproteinemia in NIDDM Patients
Authors: Juntti-Berggren Lisa , Pigon Jan , Karpe Fredrik , Hamsten Anders , Gutniak Mark , Vignati Louis , Efendic Suad
Published: March 2007

OBJECTIVE

To investigate the long-term antidiabetogenic effect of glucagon-like peptide 1 (GLP-1) and its influence on diabetic dyslipoproteinemia, patients with NIDDM were treated with GLP-1 subcutaneously for 1 week.

RESEARCH DESIGN AND METHODS

Twelve patients participated in the study. The 1st week of the study, all of them were on intensive insulin treatment and from day 8, four were randomized to a control group continuing with insulin, and eight to a treatment group where GLP-1 was given at meals together with regular insulin from day 8 to 12. On days 13 and 14, they were only given GLP-1 at meals. NPH insulin at bedtime was given throughout the study.

RESULTS

In the GLP-1-treated patients, the doses of regular insulin, given to keep a satisfactory blood glucose control, were reduced compared with treatment with insulin only. GLP-1 virtually inhibited the early increase in blood glucose after the meals, whereas an increase of ∼ 2 mmol was seen during an optimized insulin treatment. In agreement with the short half-life of the peptide, 2-h postprandial plasma insulin levels were significantly decreased both at day 12 and 14, suggesting that there was not enough GLP-1 left to stimulate endogenous insulin release and compensate for the decrease in the dose of exogenous insulin. Therefore, the effect of GLP-1 was lost before the next meal, resulting in increased preprandial blood glucose values at lunch and dinner. The concentration of VLDL triglycerides decreased already during the 1st week. This decrease persisted during the 2nd week when GLP-1 was included in the treatment. No changes were observed in the levels of LDL and HDL cholesterol. The LDL particle diameter increased from a mean of 22.3 to 22.6 nm (P < 0.01) in response to insulin treatment. A further increment to 22.9 nm (P < 0.05) was seen after GLP-1 treatment. The LDL particle size did not change in the control group. Lipoprotein lipase activity was decreased by 27% and hepatic lipase was reduced by 13% in the GLP-1-treated group.

CONCLUSIONS

We confirm the antidiabetogenic effect of GLP-1 in NIDDM patients. This effect was maintained during 7 days, which implies that the patients did not develop tolerance during this treatment period. Intensive insulin treatment, leading to normotriglyceridemia, increased the mean LDL particle diameter, which is likely to lower the risk of future coronary heart disease in patients with NIDDM. Furthermore, an additive effect of GLP-1 is indicated. Hence, this study gives additional evidence that GLP-1 may be useful as an agent for treating NIDDM.
Brainstem Auditory Evoked Potentials and Visually Evoked Potentials in Young Patients With IDDM
Authors: Seidl Rainer , Birnbacher Robert , Hauser Erwin , Bernert Günther , Freilinger Michael , Schober Edith
Published: March 2007

OBJECTIVE

To investigate whether young IDDM patients develop central nervous dysfunction and to establish a possible relationship with various disease parameters.

RESEARCH DESIGN AND METHODS

Thirty-two patients, aged 13.5 ± 2 years, with disease duration of 6 ± 2.6 years and age of onset of 7.7 ± 3.2 years (group 1), and 21 patients with short-term disease, age 9.7 ± 3.5 years, duration of disease < 2 years and age of onset of 9.4 ± 3.3 years (group 2) were compared with age- and sex-matched control subjects. Exclusion criteria were clinical signs of neuropathy, retinopathy, nephropathy, or hearing impairment. Neurophysiological studies included auditory and visually evoked potentials (EPs).

RESULTS

Patients in group 1 revealed increased P100 latencies of visually EPs (103.4 ± 4.5 vs. 96.8 ± 3.7 ms) and interpeak latencies I-V of auditory EPs (4.16 ± 0.10 vs. 3.99 ± 0.09 ms) and had abnormal latencies (values outside 2.5 SD) in 37%. However, short-term patients (group 2) had results within normal limits compared with control subjects. In group 1, longer disease duration and younger age at onset correlated with an increase of P100 latency (P < 0.001) and IPL I-V (P < 0.001). Patients with a history of severe hypoglycemic episodes had increased latencies compared with patients without hypoglycemia (P < 0.05). Furthermore, metabolic control during the last 2 years was related to P100 latencies (P < 0.05).

CONCLUSIONS

EPs noninvasively detect subclinical central nervous system involvement in children and adolescents with IDDM. Most important risk factors are duration of disease and frequency of severe hypoglycemia.
Rationale and Design of a Large Study to Evaluate the Renal and Cardiovascular Effects of an ACE Inhibitor and Vitamin E in High-Risk Patients With Diabetes: The MICRO-HOPE Study
Authors: Gerstein Hertzel C , Bosch Jackie , Pogue Janice , Taylor D Wayne , Zinman Bernard , Yusuf Salim ,   The HOPE Study investigators
Published: March 2007

OBJECTIVE

To describe the rationale and design of a large international study (microalbuminuria, cardiovascular, and renal outcomes [MICRO] in the HOPE [Heart Outcomes Prevention Evaluation] study) of an ACE inhibitor and vitamin E for the prevention of diabetic nephropathy (DN) and cardiovascular disease (CVD) in patients with diabetes and microalbuminuria (MA).

RESEARCH DESIGN AND METHODS

A total of 3,657 diabetic subjects, including 1,129 with MA, are randomly allocated to receive the ACE inhibitor ramipril (or placebo) and vitamin E (or placebo) for 4 years in a two-by-two factorial design. Diabetic subjects are a subset of the 9,541 subjects enrolled in the HOPE study.

RESULTS

The development of DN in microalbuminuric diabetic subjects and the development of MA in normoalbuminuric subjects, as well as cardiovascular death, myocardial infarction, and storke, are the main outcomes. The correlation of changes in albuminuria with changes in carotid atherosclerosis documented in a subset of subjects will also be analyzed.

CONCLUSIONS

The effect of both an ACE inhibitor and vitamin E on the progression of renal and CVD in patients with diabetes is being assessed in the MICRO-HOPE study.
Urinary Albumin Excretion as a Predictor of Diabetic Retinopathy, Neuropathy, and Cardiovascular Disease in NIDDM
Authors: Savage Susan , Estacio Raymond O , Jeffers Barrett , Schrier Robert W
Published: March 2007

OBJECTIVE

The relationship between urinary albumin excretion (UAE) and diabetic complications in NIDDM has not been studied in a large American population. The demonstrated relationship between increased UAE and the development of retinopathy, nephropathy, and neuropathy in IDDM makes this an important issue to also be studied in NIDDM patients.

RESEARCH DESIGN AND METHODS

A large population study of 947 NIDDM patients living predominantly in a metropolitan area was undertaken. Three categories of UAE, namely, normal albuminuria (< 20 μg/min), microalbuminuria (20–200 μg/min), and overt albuminuria (>200 μg/min) were compared with 1) retinopathy as assessed by stereoscopic fundus photographs; 2) cardiovascular disease as assessed by a history of cardiac disease or stroke; ischemic changes on exercise treadmill testing; Q wave myocardial infarction; Estes, Sokolow, or Cornell criteria for left ventricular hypertrophy; positive Rose questionnaire for angina; and an abnormal Doppler exam for peripheral vascular disease; and 3) neuropathy as assessed by neurological symptom and disability scores, autonomic function testing, and quantitative sensory exams involving thermal and vibratory sensation. Selected patient characteristics were then evaluated to determine their effects on the presence of diabetic complications using univariate analyses. Multiple logistic regression analyses were then performed to determine the independent effect of UAE on these diabetic complications.

RESULTS

χ2 analyses revealed that UAE was significantly associated with the presence of retinopathy (P < 0.001), neuropathy (P < 0.001), and cardiovascular disease (P < 0.001). In the multiple logistic regression analyses, UAE had strong independent associations with retinopathy, neuropathy, and cardiovascular disease.

CONCLUSIONS

Thus, increasing UAE in this large NIDDM population in the U.S. was associated with an increased prevalence of diabetic retinopathy, neuropathy, and cardiovascular disease. This suggests that UAE may be more than an indicator of renal disease in NIDDM patients and, in fact, may reflect a state of generalized vascular damage occurring throughout the body. Prospective studies in NIDDM patients are needed to determine the predictive effect of UAE and the effect of decreasing UAE on future diabetic micro- and macrovascular complications.
β-fibrinogen gene −455 G/A Polymorphism and Fibrinogen Levels: Risk factors for coronary artery disease in subjects with NIDDM
Authors: Carter Angela M , Mansfield Michael W , Stickland Max H , Grant Peter J
Published: March 2007

OBJECTIVE

To investigate the association of a G/A polymorphism at position −455 of the β-fibrinogen gene and fibrinogen levels in the development of coronary artery disease (CAD) in subjects with NIDDM.

RESEARCH DESIGN AND METHODS

In 187 Caucasian subjects with NIDDM, presence of CAD was taken as a clinical history of angina, myocardial infarction, coronary angioplasty, or coronary artery bypass grafting, confirmed from medical case notes.

RESULTS

Fibrinogen levels were significantly higher in subjects with CAD (n = 38, 3.41 [3.12–3.73] g/l) than those without (n = 149, 2.99 [2.87–3.11] g/l, P = 0.004 [geometric mean, 95% CI]). Comparing the genotype frequencies by X2 testing, there was a significant difference between subjects with CAD (GG = 0.84, GA + AA = 0.16) and those without (GG = 0.64, GA + AA = 0.36, P = 0.02). In a logistic regression model, including age, BMI, cholesterol, sex, smoking, triglycerides, and plasminogen activator inhibitor antigen as covariates, genotype and fibrinogen levels were significantly associated with CAD. The odds ratio for having CAD in individuals homozygous for the G allele compared with those possessing the A allele was 1.77 (1.08−2.90), P = 0.03; and for an increase of 1 g/l in fibrinogen levels was 1.60 (1.00–2.60), P = 0.05.

CONCLUSIONS

These data suggest a relationship between the −455 G/A β-fibrinogen gene polymorphism and the development of CAD in subjects with NIDDM. This relationship was not associated with variations in fibrinogen levels, suggesting that this polymorphism may be in linkage with a polymorphism within the coding region of the β-fibrinogen gene, which results in an alteration in the stability of the fibrin clot.
Age-Specific Incidence and Duration of Known Diabetes: The Cremona Study
Authors: Garancini Maria Paola , Gobbi Cecilia , Errera Antonino , Sergi Alessandro , Gallus Giuseppe
Published: March 2007

OBJECTIVE

To estimate the overall and age-specific incidence of known diabetes and its total duration through prevalence data and to assess the consistency of the results by mortality analysis of the same cohort.

RESEARCH DESIGN AND METHODS

Two different sources were used. The first was a representative sample of 2,274 prevalent known-diabetic subjects. These data provided overall and age-specific incidence estimates by fitting a logistic model to the partial incidence rates for different diagnosis cohorts and to the disease duration. The age at diagnosis structure was built from the age-specific estimates. Prevalence data also provided total duration estimates by converting the prevalent duration-to-date structure into an incident total duration structure. The second source was 145 deceased subjects who were taken from the 6-year follow-up sample of 1,132 prevalent subjects. The age at diagnosis and estimates of total disease duration were provided for these subjects, who paralleled the characteristics of the incident cohort.

RESULTS

The two independent estimates of total disease duration were similar (prevalent subjects, 15.7 years; deceased subjects, 14.1 years): the average duration was 14.9 years. The ratio between prevalence and total duration yielded an independent yearly incidence estimate of 2.2 per 1,000 person-years (men, 2.0; women, 2.4), which was close to the value given by the model of 2.1 per 1,000 person-years (men, 1.9; women, 2.3). Also, the independently determined age structures overlapped, and their average was used to calculate the age-specific incidence. Incidence was negligible for individuals <30 years of age, and it was about 6.0 per 1,000 person-years for individuals >50 years of age.

CONCLUSIONS

This study provided reliable estimates of NIDDM age-specific incidence rates and total disease duration, data that are seldom investigated in this type of disease.
The Dietary Intake of Children With IDDM
Authors: Randecker Greg A , Smiciklas-Wright Helen , McKenzie Jeannie M , Shannon Barbara M , Mitchell Diane C , Becker Dorothy J , Kieselhorst Kessey
Published: March 2007

OBJECTIVE

To assess the dietary intake of children with IDDM and to determine whether the intake meets the current nutritional recommendations for children with IDDM.

RESEARCH DESIGN AND METHODS

A total of 66 children with IDDM who were < 10 years of age were recruited from two suburban Pennsylvania hospitals. To collect dietary intake data, subjects were asked, via telephone interview, to complete three random-day 24-h dietary recalls. Data were analyzed for the content of nutrients and other food components by a computerized database program. Intakes were expressed as a 3-day average intake for each subject.

RESULTS

Overall mean intake of protein and cholesterol approximated the current recommendations. The mean intake of saturated fat exceeded recommendations, while fiber intake was < the recommended level. Many of the children consumed levels of saturated fat well above recommendations. Energy, vitamin, and mineral intakes were adequate for the overall sample. However, from 10 to 40% of the sample had an inadequate intake of vitamin D, vitamin E, and zinc. The percentage of those with inadequate intakes of these nutrients decreased with age.

CONCLUSIONS

These data suggest that, on average, among this sample of children with IDDM aged < 10 years, adherence to the current nutritional recommendations for children with IDDM was adequate, but some individual children had intakes that were not consistent with the recommendations for optimal management of IDDM.
Cellular Ions in NIDDM: Relation of Calcium to Hyperglycemia and Cardiac Mass
Authors: Barbagallo Mario , Gupta Raj K , Resnick Lawrence M
Published: March 2007

OBJECTIVE

To investigate the role of hyperglycemia in mediating the clinical association of NIDDM with hypertension and left ventricular dysfunction and hypertrophy.

RESEARCH DESIGN AND METHODS

Since hyperglycemia elevates cytosolic free calcium (Cai) both in myocardial and vascular smooth muscle cells, we utilized nuclear magnetic resonance (NMR) spectroscopy to measure erythrocyte Cai levels and compared them with serum ionized calcium (Caio), glucose, and insulin values before and following an oral glucose tolerance test (OGTT) and with previously obtained cardiac structural indexes in normotensive and hypertensive NIDDM (n = 32) and normal control subjects (n = 35).

RESULTS

Compared with control subjects, normotensive NIDDM subjects had higher Cai (31.5 ± 2.3 vs. 24.3 ± 1.9 nmol/l, P = 0.05), lower intracellular free magnesium (Mgi) (200 ± 10 vs. 225 ± 7 μumol/l, P = 0.05), and greater posterior wall thickness (0.98 ± 0.04 vs. 0.86 ± 0.03 cm, P = 0.05). Hypertensive NIDDM subjects exhibited a further increase in Cai (43.1 ± 4.4 nmol/l, P = 0.05 vs. control subjects) and left ventricular mass (LVM) (201.5 ± 12.2 vs. 155.8 ± 7.7 g, P = 0.05 vs. control subjects). For all subjects, significant relationships were observed between Cai and fasting blood glucose (r = 0.510, P < 0.01), HbA1c (r = 0.389, P < 0.05), and the glycemic response to OGTT (the area under the curve [AUC] for glucose; r = 0.519, P < 0.01) and to systolic (r = 0.504, P < 0.01) and diastolic (r = 0.624, P < 0.01) blood pressure. Left ventricular mass index (LVMI) was related to fasting glucose levels (r = 0.406, P < 0.01) and the AUC for glucose (r = 0.380, P < 0.01), but not to fasting insulin or insulin responses to an OGTT. The LVMI was best related to Cai (r = 0.516, P < 0.01), while being inversely related to Caio (r = −0.486, P < 0.01). Multivariate regression indicated the contribution of glucose to LVMI was independent of age, BMI, insulin, and blood pressure but demonstrated a significant interaction with Cai.

CONCLUSIONS

Altogether, these data suggest that glucose-related excess Cai is a fundamental lesion in diabetes that contributes to the elevated blood pressure and cardiac mass in this disease.
NIDDM, Impaired Glucose Tolerance, and Pulmonary Function in Older Adults: The Rancho Bernardo Study
Authors: Barrett-Connor Elizabeth , Frette Catherine
Published: March 2007

OBJECTIVE

To determine whether NIDDM or plasma glucose level in subjects without diabetes is associated with reduced pulmonary function in 525 men and 714 women, 51–95 years of age.

RESEARCH DESIGN AND METHODS

The analysis was based on data from a community-based study, the Rancho Bernardo Study. Between 1984 and 1987, 82% of community-dwelling residents had an oral glucose tolerance test. Between 1988 and 1991, 80% had lung function assessed by spirometry (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]).

RESULTS

In analyses adjusted for age, height, and cigarette smoking, pulmonary function was not associated with known or newly diagnosed NIDDM in men or women. However, FEV1 and FVC were each independently reduced in men with diabetes of 10 or more years' duration. Fasting plasma glucose (FPG) levels were correlated with FEV1 and FVC in men without diabetes. No associations were found in women.

CONCLUSIONS

The overall absence of an association of NIDDM with pulmonary function in these older adults may reflect survival bias and the small number of subjects with severe diabetes or diabetes of prolonged duration. The apparent relation of FPG levels to FEV1 and FVC suggests that any effect of glycemia precedes diabetes and contradicts any putative causal role for duration and severity of glycemia, however. More epidemiological studies are needed to provide further information about the relationship between NIDDM and lung function.
Retinopathy Predicts Coronary Heart Disease Events in NIDDM Patients
Authors: Miettinen Heikki , Haffner Steven M , Lehto Seppo , Rönnemaa Tapani , Pyörälà Kalevi , Laakso Markku
Published: March 2007

OBJECTIVE

Proliferative retinopathy has been shown to be associated with increased all-cause mortality in diabetic patients. We assessed the relationship between the different degrees of retinopathic changes at baseline and serious coronary heart disease (CHD) events (CHD death or nonfatal myocardial infarction) in a prospective population-based study of NIDDM patients.

RESEARCH DESIGN AND METHODS

Our study is based on the 7-year follow-up cohort of 1,059 NIDDM patients in east and west Finland. Classification of retinopathic changes was based on clinical examination of fundi, and the findings were classified to three categories according to the status of the worse eye: no retinopathic changes, background retinopathy, and proliferative retinopathy.

RESULTS

During the 7-year follow-up, 255 (24%) patients developed serious CHD event. In patients with proliferative retinopathy at baseline, the risk of CHD events during the follow-up was statistically significantly higher compared with patients without retinopathic changes (odds ratio [OR] 2.31, 95% CI 1.21–4.40). The association between proliferative retinopathy and CHD events remained significant when other cardiovascular risk factors were controlled for.

CONCLUSIONS

Proliferative retinopathy in NIDDM patients was associated with CHD events. Our findings suggest that retinopathy and CHD may have similar pathophysiological backgrounds.
Phenformin-Associated Lactic Acidosis Due to Imported Phenformin
Authors: Lu Hua Chung , Parikh Purvi P , Lorber Daniel L
Published: March 2007

OBJECTIVE

To emphasize the continued incidence of phenformin-associated lactic acidosis.

CASE REPORT

We report a case of phenformin-associated lactic acidosis in a Chinese man who received phenformin while in China. Diagnosis was made; the patient was treated appropriately and survived.

COMMENTS

Phenformin-associated lactic acidosis may still occur in the U.S.
Proinsulin Immunoreactivity in Recent-Onset IDDM: The significance of insulin antibodies and insulin autoantibodies
Authors: Snorgaard Ole , Kjems Lise L , Røder Micheal E , Hartling Svend G , Dinesen Bo , Binder Christian
Published: March 2007

OBJECTIVE

To study the natural history of fasting proinsulin immunoreactivity (PIM) during the first 30 months of IDDM and its relationship to fasting C-peptide and insulin antibodies.

RESEARCH DESIGN AND METHODS

An incidence cohort of 204 consecutive newly diagnosed IDDM patients were followed prospectively, having blood drawn for measurements at diagnosis and at 1, 3, 6, 9, 12, 18, 24, and 30 months. A sensitive enzyme-linked immunosorbent assay was used for the determination of PIM.

RESULTS

All patients had detectable fasting PIM in plasma at diagnosis, with a median value and interquartile range of 3.5 pmol/l (2.2–6.2). The median PIM level increased during the first months of IDDM to reach a peak at 9–12 months (9.9–10.3 pmol/l). PIM then declined gradually to 5.6 pmol/l (1.9–13.5) at 30 months without reaching baseline. PIM at each time point was widely scattered in a skewed log-normal distribution without signs of bimodality. After the onset of insulin treatment, median insulin antibody level increased and declined in a similar pattern. Both PIM and antibody level were significantly higher in children and adolescents compared with adults. However, stepwise multiple regression analysis showed that age was only of minor importance for the PIM variation during the study period. Insulin antibody level and fasting C-peptide were the major determinants at 3–30 months, accounting for ∼40% of the variation (R2). Blood glucose was of minor importance, and insulin dose, HbA1c, and BMI were of no importance. The correlation between fasting PIM and fasting C-peptide improved (R2 doubled) if the insulin antibody level was accounted for. Further, the slope of the correlation curve between PIM and C-peptide increased threefold when antibody binding was > 4%. At diagnosis, insulin autoantibodies could be detected in 19% of the patients. Their presence predicted higher proinsulin at 1–3 months, a higher insulin dose the 1st year, and higher levels of insulin antibodies later in the study.

CONCLUSIONS

Circulating insulin antibodies may affect the level of PIM in IDDM, probably by adding a pool of IgG-bound PIM thereby increasing half-life and plasma concentration. This may explain why C-peptide and PIM levels do not change in concert during the 1st years of IDDM. Unlike C-peptide, PIM can not therefore quantitate β-cell secretion unless the presence of insulin antibodies is ruled out.