Exploring Treatment Strategies for Type 2 Diabetes

Bloomgarden, Zachary T.

doi:10.2337/dc07-zb10

Cited by 21 publications

(9 citation statements)

References 54 publications

(40 reference statements)

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“…Our data suggest that PBCF is an important therapeutic target in controlling glucose excursions during postprandial periods to prevent secondary complications of type 2 diabetes. In this regard, treatment regimens including incretin mimetics (22,25) might have the potential of longer-term improvement in PCBF.…”

Section: Discussionmentioning

confidence: 99%

Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents

Kohnert

Augstein

Zander³

et al. 2009

Diabetes Care

106

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OBJECTIVEGlucose fluctuations trigger activation of oxidative stress, a main mechanism leading to secondary diabetes complications. We evaluated the relationship between glycemic variability and β-cell dysfunction.RESEARCH DESIGN AND METHODSWe conducted a cross-sectional study in 59 patients with type 2 diabetes (aged 64.2 ± 8.6 years, A1C 6.5 ± 1.0%, and BMI 29.8 ± 3.8 kg/m2[mean ± SD]) using either oral hypoglycemic agents (OHAs) (n = 34) or diet alone (nonusers). As a measure of glycemic variability, the mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring data recorded over 3 consecutive days. The relationships between MAGE, β-cell function, and clinical parameters were assessed by including postprandial β-cell function (PBCF) and basal β-cell function (BBCF) obtained by a model-based method from plasma C-peptide and plasma glucose during a mixed-meal test as well as homeostasis model assessment of insulin sensitivity, clinical factors, carbohydrate intake, and type of OHA.RESULTSMAGE was nonlinearly correlated with PBCF (r = 0.54, P < 0.001) and with BBCF (r = 0.31, P = 0.025) in OHA users but failed to correlate with these parameters in nonusers (PBCF P = 0.21 and BBCF P = 0.07). The stepwise multiple regression analysis demonstrated that PBCF and OHA combination treatment were independent contributors to MAGE (R2 = 0.50, P < 0.010), whereas insulin sensitivity, carbohydrate intake, and nonglycemic parameters failed to contribute.CONCLUSIONSPBCF appears to be an important target to reduce glucose fluctuations in OHA-treated type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents

Kohnert

Augstein

Zander³

et al. 2009

Diabetes Care

106

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“…T2D is a disease characterized by reduced insulin sensitivity in peripheral tissues and secretion from pancreatic β-cells [5]. The fa/fa rats showed remarkable hyperinsulinemia at 5-11 weeks of age, but after 11 weeks of age, no significant difference in plasma insulin levels compared to the original lean rats.…”

Section: ± 02 G In Lean Ratsmentioning

confidence: 99%

“…Type 2 diabetes (T2D) is a major global health problem, and rapidly increasing in prevalence worldwide [3,9,10,14]. T2D is a multifactorial disease caused by a hormonal imbalance between insulin secretion and peripheral insulin sensitivity [5]. Animal models of T2D are useful to elucidate the pathogenesis of the disease and to evaluate the therapeutic activity of new medications.…”

mentioning

confidence: 99%

Plasma Profiles of Glucose, Insulin and Lipids in the Male WBN/Kob-<i>Lepr<sup>fa</sup></i> Rat, a New Model of Type 2 Diabetes with Obesity

Kaji

Okuno

Ohno-Ichiki

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRACT. Plasma profiles of glucose, insulin and lipids were examined in the male WBN/Kob-Lepr fa (fa/fa) rat, a new model of type 2 diabetes (T2D), in comparison with age-matched original male WBN/Kob (lean) rats. The fa/fa rats developed hypertriglycemia, obesity and hyperglycemia from 5, 7, and 9 weeks of age, respectively. Plasma insulin levels in fa/fa rats were significantly higher than those in lean rats at 5 weeks of age, but after 11 weeks of age gradually declined to the levels in lean rats. HOMA-IR, a measure of insulin resistance status, showed that fa/fa rats had insulin resistance. The fa/fa rat has the potential to become an important animal model of T2D with obesity. Type 2 diabetes (T2D) is a major global health problem, and rapidly increasing in prevalence worldwide [3,9,10,14]. T2D is a multifactorial disease caused by a hormonal imbalance between insulin secretion and peripheral insulin sensitivity [5]. Animal models of T2D are useful to elucidate the pathogenesis of the disease and to evaluate the therapeutic activity of new medications. The currently established rodent T2D models are divided into 2 broad categories: experimentally induced nonspontaneous models, and genetically induced spontaneous models.The WBN/Kob-Lepr fa (fa/fa) rat is a new congenic strain that has been developed by introducing the fa gene of the Zucker fatty (ZF) rat into the original WBN/Kob (lean) rat genome [1,2]. The male, but not female, lean rat is a hereditary model of diabetes mellitus and chronic pancreatitis [13,15]. The leptin receptor fatty gene (Lepr fa ) is a recessive mutation which was reported as a cause of obesity in ZF rats which exhibit hyperphagia resulting from a deficiency of leptin receptor signaling followed by obesity, hyperinsulinemia and dyslipidemia [6,11,16]. The fa/fa rat has been reported as a model of T2D with obesity [1, 2], but little is known about profiles of plasma insulin and lipids in this strain. In order to further characterize the fa/fa rat as a T2D model, we evaluated the plasma profiles of glucose, insulin and lipids in fa/fa rats in comparison with those in lean rats.Male WBN/Kob-Lepr fa (fa/fa) rats and age-matched male WBN/Kob (lean) rats (Japan SLC Inc., Shizuoka, Japan) were used in the present study. The fa/fa rats were confirmed by genotyping of the fa locus, performed according to a PCR-restriction fragment length polymorphism method [8]. The rats were housed in a climate-controlled room with a temperature of 23 ± 3°C, humidity of 55 ± 5%, and 12-hr lighting cycle. A commercial rat chow (CRF-1 ® , Oriental Yeast, Tokyo, Japan) and water were provided ad libitum. All study protocols were approved by the Animal Research Committee of Azabu University.Body weight and plasma levels of glucose, insulin, triglyceride (TG) and non-esterified fatty acids (NEFA) were analyzed in rats from the age of 5 weeks to 19 weeks at 2-week intervals. Blood was collected from the tail vein of non-fasted conscious rats into a heparinized glass capillary, and centrifuged to remove plasma. P...

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“…When a new-onset type 2 diabetic patient presents with severe hyperglycemia, there are defects in insulin secretion and action, which is optimally treated with aggressive insulin injections (8,9). After the symptoms have been relieved, it may be possible to withdraw insulin and shift to oral agents.…”

mentioning

confidence: 99%

Beneficial Effects of Insulin on Glycemic Control and β-Cell Function in Newly Diagnosed Type 2 Diabetes With Severe Hyperglycemia After Short-Term Intensive Insulin Therapy

Wu²,

et al. 2008

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OBJECTIVE -To evaluate whether treatment with insulin is advantageous compared with oral antidiabetes agents in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy.RESEARCH DESIGN AND METHODS -Newly diagnosed type 2 diabetic patients with severe hyperglycemia were hospitalized and treated with intensive insulin injections for 10 -14 days. The oral glucose tolerance test (OGTT) was performed after intensive insulin treatment. After discharge, the patients were randomized to receive either insulin injections or oral antidiabetes drugs (OADs) for further management. The OGTT was repeated 6 months later, and ␤-cell function and insulin sensitivity were evaluated again. These subjects were continually followed up for another 6 months to evaluate their long-term glycemic control.RESULTS -At the 6th month of the study, the A1C level was significantly lower in the insulin group than in the OAD group (6.33 Ϯ 0.70% vs. 7.50 Ϯ 1.50%; P ϭ 0.002). During the follow-up visit, the A1C level was still better in the insulin group (6.78 Ϯ 1.21% vs. 7.84 Ϯ 1.74%; P ϭ 0.009). All parameters regarding ␤-cell function measured in the OGTT were improved significantly in both groups after 6 months of treatment. Compared with the OAD group, the homeostasis model assessment of ␤-cell function index, insulin area under the curve, and insulinogenic index were better in the insulin group. CONCLUSIONS -A 6-month course of insulin therapy, compared with OAD treatment, could more effectively achieve adequate glycemic control and significant improvement of ␤-cell function in new-onset type 2 diabetic patients with severe hyperglycemia.

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Exploring Treatment Strategies for Type 2 Diabetes

Cited by 21 publications

References 54 publications

Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents

Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents

Plasma Profiles of Glucose, Insulin and Lipids in the Male WBN/Kob-<i>Lepr<sup>fa</sup></i> Rat, a New Model of Type 2 Diabetes with Obesity

Beneficial Effects of Insulin on Glycemic Control and β-Cell Function in Newly Diagnosed Type 2 Diabetes With Severe Hyperglycemia After Short-Term Intensive Insulin Therapy

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