Diabetes & Metabolism Journal

Review

Challenges in Diagnosing Type 1 Diabetes in Different Populations: Marian Rewers; Diabetes Metab J. 2012;36(2):90-97. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.90

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Diabetes affects today an estimated 366 million people world-wide, including 20 million to 40 million of patients with type 1 diabetes (T1D). While T1D accounts for 5% to 20% of those with diabetes, it is associated with higher morbidity, mortality and health care cost than the more prevalent type 2 diabetes. Patients with T1D require exogenous insulin for survival and should be identified as soon as possible after diagnosis to avoid high morbidity due to a delay in insulin treatment. It is also important to present to the patient correct prognosis that differs by the type of diabetes. From the research point of view, correct classification should help to identify the etiologies and to develop specific prevention for T1D. This review summarizes evidence that may be helpful in diagnosing T1D in various ethnic groups. Challenges in interpretation of results commonly used to determine the type of diabetes are highlighted.

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Original Articles

Effects of Resistance Training and Aerobic Exercise on Insulin Sensitivity in Overweight Korean Adolescents: A Controlled Randomized Trial: Sunghwan Suh, In-Kyong Jeong, Mi Yeon Kim, Yeon Soo Kim, Sue Shin, Sun Sin Kim, Jae Hyeon Kim; Diabetes Metab J. 2011;35(4):418-426. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.418

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Abstract PDF PubReader

Background

Data on the impact of resistance training on insulin resistance in overweight or obese children are inconclusive.

Methods

Thirty overweight South Korean adolescents (mean age of 13.10 years) were divided by sex, and then randomly assigned to one of three treatment groups, which were the diet only (DO), diet with aerobic exercise (AE), or diet with resistance training (RT) group. Physiologic and metabolic parameters were assessed at baseline and after 12 weeks of exercise training and diet modification.

Results

Both exercise groups (aerobic and resistance) showed significant improvements in their insulin area under the curve and insulin sensitivity index values when compared to their baseline values while the DO group showed no significant changes in these variables. Age-, sex-, and body mass index (BMI)-adjusted intergroup comparison analyses showed a marked reduction in BMI and a significant reduction in muscle mass in the AE group when compared to the RT group and the DO group, respectively.

Conclusion

A 12-week exercise training program of either resistance or aerobic activity improved insulin sensitivity in overweight adolescents, although it failed to show superiority over a DO program. Aerobic exercise decreased both body weight and BMI, and it was noted that this group also had a significant reduction in muscle mass when compared to the DO group.

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Effects of Eight Weeks of Combined Training with Antioxidant Vitamins E and C on Glutathione, Glutathione Peroxidase, and Superoxide Dismutase in the Heart Tissue of Streptozotocin-induced Diabetic Rats
Elaheh Heydarnia, Farzaneh Taghian, Khosro Jalali Dehkodi, Mehrzad Moghadasi
Gene, Cell and Tissue.2021;[Epub] CrossRef
Effect of resistance training with and without caloric restriction on visceral fat: A systemic review and meta‐analysis
Mousa Khalafi, Abbas Malandish, Sara K. Rosenkranz, Ali A. Ravasi
Obesity Reviews.2021;[Epub] CrossRef
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Samiya Noreen, Muhammad Shafique, Tayyaba Mustafa Mian, Hafiz Abdul Rehman, Abdul Rehman, Muhammad Saad Shafiq, Ibraheem Zafar, Ramsha Masood
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Does exercise training affect resting metabolic rate in adolescents with obesity?
Angela S. Alberga, Denis Prud’homme, Ronald J. Sigal, Gary S. Goldfield, Stasia Hadjiyannakis, Réjeanne Gougeon, Penny Phillips, Janine Malcolm, George A. Wells, Steve Doucette, Jinhui Ma, Glen P. Kenny
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The Effect of Rosiglitazone on Gluose Metabolism and Insulin Sensitivity in Non Obese Type 2 Diabetic Rat Models.: Mi Jin Kim, Eui Jong Chung, Byung Wook Ha, Ji Hoon Kim, Su Min Nam, Mi Young Lee, Jang Hyun Kho, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2007;31(4):319-325. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.319

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Abstract PDF: BACKGROUND
In Korea, most of type 2 diabetic patients are non obese. We made non obese type 2 diabetic rat models, which were characterized by insulin resistance and insulin secretion defect. Our study aimed to investigate the effect of rosiglitazone on glucose metabolism and insulin sensitivity in non obese type 2 diabetic rat models. Furthermore, we may estimate the effect of rosiglitazone treatment in non obese type 2 diabetic patients in Korea. METHODS: 20 male newborn (12 hours old) Sprague-Dawley rats were made diabetes by streptozotocin (75 mg/kg, intraperitoneal injection). At 16 weeks old, diabetes were confirmed by intraperitoneal glucose tolerance test (IPGTT, 30% D/W, 2 kg/kg). After that, diabetic groups were divided into two groups. One group was fed on normal chow and rosiglitazone (3 mg/kg/day) and the other group was fed on normal chow for eight weeks. At the age of 24 weeks, we measured body weight (BW), plasma glucose, insulin, C-peptide levels. And we performed IPGTT and insulin tolerance test (ITT) in two groups. Thereafter, we determined the insulin content of pancreas and epididymal fat weight. RESULTS: Body weight was significantly higher in rosiglitazone group than control group. On IPGTT, plasma glucose, insulin and C-peptide levels were not significantly different between two groups. But, on insulin tolerance test, Kitt (%/min) values of rosiglitazone group were significantly higher than control group (2.7 vs. 1.8). The insulin content of pancreas and epididymal fat weight was not different between two groups. CONCLUSION: These results suggested that rosiglitazone improved insulin sensitivity in non obese type 2 diabetes rat models independent of glucose level.

Usefulness of Insulin Sensitivity Indexes derived from Oral Glucose Tolerance Test in Women with Polycystic Ovary Syndrome.: Hyo Jeong Kim, Eun Kyung Byun, Jee Young Oh, Yeon Ah Sung, Hye Won Chung; Korean Diabetes J. 2006;30(4):277-284. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.277

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Abstract PDF

BACKGROUND
Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and it makes them to have high risk for development of type 2 diabetes. Evaluation of insulin sensitivity would be important to predict their risks. Although the euglycemic-hyperinsulinemic clamp technique is the gold standard for measuring insulin sensitivity, it is too hard to practice in large epidemiologic studies. The aim of this study is to verify the validity of various insulin sensitivity indexes from oral glucose tolerance test (OGTT) in women with PCOS. METHODS: We performed euglycemic-hyperinsulinemic clamp (target glucose; 90 mg/dL, insulin ;~1 mU/kg.min) to obtain insulin-mediated glucose disposal rate (M-value) in 62 non-diabetic women with PCOS (BMI < 23 kg/m2; n = 37, BMI > or = 23 kg/m2; n = 25). Homeostasis model assessment [HOMA(IR)], quantitative insulin sensitivity check index (QUICKI), glucose to insulin ratio (G/I ratio), whole body insulin sensitivity index [ISI(COMP)], metabolic clearance rate of glucose [MCR(est)-OGTT(1,2)], and insulin sensitivity indexes [ISI(est)-OGTT(1,2)] were calculated from plasma glucose and insulin levels from standard 75-g OGTT. The correlations of various insulin sensitivity indexes from OGTT with M-value were evaluated. RESULTS: In lean women with PCOS (BMI < 23 kg/m2, n = 37), ISI(COMP) (r = 0.36, P < 0.05), MCRest-OGTT1 (r = 0.49, P < 0.01), ISI(est)-OGTT(1) (r = 0.50, P < 0.01), MCR(est)-OGTT(2) (r = 0.45, P < 0.01) and ISI(est)-OGTT(2) (r = 0.40, P < 0.05) were significantly correlated with M-value. In overweight and obese women with PCOS (BMI > or = 23 kg/m2, n = 25), HOMA(IR) (r = -0.40, P < 0.05), QUICKI (r = 0.40, P < 0.05), MCR(est)-OGTT(1) (r = 0.76, P < 0.001), ISI(est)-OGTT(1) (r = 0.63, P < 0.001), MCR(est)-OGTT(2) (r = 0.58, P < 0.01) and ISI(est)-OGTT(2) (r = 0.42, P < 0.05) showed significant correlations with M-value. CONCLUSION: MCR(est)-OGTT(1) and ISI(est)-OGTT(1) were the most reliable and easily accessible insulin sensitivity indexes obtained from OGTT for measuring of insulin sensitivity in women with PCOS regardless of obesity.

Citations

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Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes
Flavia Tosi, Enzo Bonora, Paolo Moghetti
Human Reproduction.2017; 32(12): 2515. CrossRef

Effects of Aging and Obesity on Insulin Secretion and Sensitivity.: J Y Kim, J H Jee, H J Kim, B W Lee, Y J Chung, J H Chung, Y K Min, M S Lee, M K Lee, K W Kim; Korean Diabetes J. 2005;29(1):39-47. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is occurring in epidemic proportions worldwide and aging has been defined as one of the risk factors for the progression to diabetes. The mechanism responsible for deterioration of glucose tolerance with aging is still unclear. It has been debated whether this deterioration results from an abnormal beta cell secretory function or/and decreased insulin sensitivity, from the aging process per se, or some other factors, such as an increase in BMI and abdominal fat. The changes in the insulin secretion and sensitivity were assessed in relation to aging and obesity, and the association between obesity and factors influencing glucose homeostasis in obese subjects evaluated. METHODS: 530 individuals, aged 24 to 75 years, having undergone a 75 g OGTT were enrolled, and the insulinogenic index and HOMA-IR calculated for each subject. 212 individuals were obese, i.e. a BMI above 25, which was evaluated from the body composition by CT at the umbilicus and thigh levels. RESULTS: There was negative correlation between the insulinogenic index and age, but not between HOMA-IR and age. In relation to increasing age, the body composition changed toward a metabolically obese state, with increasing WHR, visceral fat area, VSR and VWR. Both the insulinogenic index and HOMA-IR were positively correlated with the anthropometric parameters. CONCLUSION: The age-associated deterioration in glucose tolerance may be due to decreases in both insulin secretion and insulin sensitivity from changes in body composition

Effect of Captopril on Insulin Sensitivity for Subjects with Insulin Resistance.: Hye Jung Lee, Hyuk Sang Kwon, Jin Hee Lee, Sung Koo Kang, Yoon Hee Choi, Sung Ha Hwang, Seung Hyun Ko, Jung Min Lee, Kun Ho Yoon, Bong Yun Cha, Won Chul Lee, Kwang Woo Lee, Ho Young Son; Korean Diabetes J. 2004;28(5):416-424. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors are becoming increasingly popular as the first-choice antihypertensive agents for diabetic patients. This could be partly related to their suggested beneficial effects on insulin sensitivity. This study was designed to compare the effect of captopril with that of control (nitrendipine) on insulin sensitivity for subjects with insulin resistance. METHODS: 24 subjects, aged less than 60 years, with their insulin resistance being defined as the area under the curve (AUCi) of insulin that was 2 standard deviations (SD) more than that of the control subjects during oral glucose tolerance test were recruited. A randomized, double-blind, crossover trial was conducted for an 8 weeks treatment period with captopril and the control (nitrendipine) that was given after an initial 6 weeks run-in period. Anthropometric measurement including weight, height, waist and hip circumference, blood pressure (systolic & diastolic), lipid profile blood chemistry, electrolytes levels & renal function testing, and frequently sampled intravenous glucose tolerance tests (FSIGT) for the insulin sensitivity index (SI) & acute insulin response to glucose (AIRg) were also done before and after treatment, respectively. RESULTS: 18 subjects (6 males, 12 females) completed the study. The mean age of the study subjects was 47.9+/-2.9 years (mean+/-SEM), and their BMI was 28.0+/-0.7 kg/m2 (mean+/-SEM).There was a significant decrease in weight (baseline; 71.5+/-9.2 kg vs. captopril; 70.7+/-9.0 kg and nitrendipine; 709+/-9.2 kg, p<0.05, respectively) and BMI (baseline; 28.0+/-3.0 kg/m2 vs. captopril; 27.7+/-2.8 kg/m2 and nitrendipine; 27.8+/-2.9 kg/m2, p<0.05, respectively) for both groups compared with the baseline, but there are no significant differences between the two groups. Triglyceride was significantly decreased after treatment with captopril compared to the baseline and nitrendipine (187.0+/-99.5 mg/dL vs. 224.5+/-134.2 mg/dL, respectively, p<0.05). The SI was significantly increased after captopril treatment compared with the baseline (1.4+/-1.0 vs. 2.5+/-0.8 min-1 per mU/ml, respectively, p<0.05), and the captopril group was significantly higher than that of nitrendipine (1.5+/-1.0 min-1 per mU/ml, p <0.05). Acute insulin response to glucose in both groups was also increased after treatment, but there was no statistically significance. CONCLUSION: Captopril therapy improved insulin sensitivity, and it decreased the concentration of fasting insulin in subjects with insulin resistance.

Insulin Secretory Dysfunction in the Pathogenesis of Type 2 Diabetes in Koreans: A Minimal Model Analysis.: Sung Hoon Kim, Dong Jun Kim, Byung Wan Lee, In Ah Seo, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee; Korean Diabetes J. 2003;27(5):414-419. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Type 2 diabetes is a complex, heterogeneous disorder, characterized by impairments in both insulin secretion and insulin action. This study was done to examine the significance of alterations in insulin sensitivity and beta-cell function in the pathogenesis of type 2 diabetes in Korean subjects with varying degrees of glucose intolerance. METHODS: Forty Korean subjects were studied, 12 with normal glucose tolerance (NGT), 14 with impaired glucose tolerance (IGT) and 14 with type 2 diabetes. An oral glucose tolerance test (OGTT) was performed on each subject. Insulin sensitivity (SI), glucose effectiveness (Sg), acute insulin response after intravenous glucose (AIRg) and the disposition index (DI= SI x AIRg) were measured by the insulin-modified, frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Neither fasting serum insulin level nor SI was significantly different among the NGT, lGT and diabetes groups. Sg was significantly lower in the type 2 diabetes group than in the NGT group. The mean AIRg was blunted in the IGT and diabetes groups when compared with the NGT group. DI was more powerful in differentiating between NGT and IGT, compared to AIRg alone. CONCLUSION: These findings suggest that a defect in the compensatory insulin secretion might be more important than insulin resistance in the development of type 2 diabetes in Korean subjects.

The Role of Chromium as an Insulin Sensitizer in Rats Receivieng Corticosteroid.: Dong Sun Kim, Chang Beom Lee, Yong Soo Park, You Hern Ahn, Tae Wha Kim, Ho Soon Choi, Il Kyu Park, Hyun Jin Shin, Ju Seop Kang; Korean Diabetes J. 2001;25(3):211-217. Published online June 1, 2001

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Abstract PDF: BACKGROUND
Chromium (Cr) has been known to be essential for the regulation of insulin action. Recently it has been reported that corticosteroid increases urinary loss of Cr, and that Cr supplementation recovers steroid induced diabetes mellitus. METHODS: Rats were daily treated with dexamethasone (0.2 mg/kg, ip) for first 7 days and were further treated daily with dexamethasone plus either chromium picolinate (30 mg/kg) or a placebo for a period of 14 days. RESULTS: At the end of experiment (Day 21), the control rats treated only with dexamethasone weighed 320 gram (80% of initial weight) in average, but the Cr treated rats weighed 364 gram (91% of initial weight. p<0.05). An insulin sensitivity test [subcutaneous injection of insulin (5 U/kg) plus intraperitoneal injection of glucose (30 minutes after insulin injection)] were conducted. During the insulin sensitivity tests, the area under curves (AUC(0->120 min)) of the time-glucose concentrations curves in the Cr-treated group were decreased compared to those in the control group (5250 vs 15883 mg-min/dL, p<0.01). Fasting serum insulin levels in the Cr-treated rats were clearly decreased by 46.9% compared to those in the control group (2.98 vs 5.60 ng/mL, p<0.05). CONCLUSIONS: We conclude that chromium supplementation reverse a catabolic state, and increase insulin sensitivity in dexamethasone treated rats.

The Combined Effects of Protein Malnutrition and Chronic Alcohol lntake on lnsulin Secretion and Sensitivity in Growing Rats.: Bong Soo Cha, Chul Woo Ahn, Hae II Lee, Yong Seok Yoon, Jae Kyeung Sung, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(1):19-36. Published online January 1, 2001

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Abstract PDF: BACKGROUND
This investigation was performed to examine the combined effects of protein malnutrition and chronic moderate amount of alcohol intake on insulin secretory capacity and sensitivity in growing rats. METHODS: Weanling 4-week-old male Sprague-Dawley rats were fed low protein [5%, (wt/wt)] or control (C, 20%) diet from 4 to 12 weeks and alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into the 4 groups according to different diet protocols: group 1 (protein-deficient alcohol rats), group II (protein-deficient saline rats), group III (protein-sufficient alcohol rats), and group IV (protein-sufficient saline or control rats), At the age of 12 weeks, we determined the insulin secretory capacity and sensitivity in the 4 different diet groups. RESULTS: The results are summarized as following: 1. Normal weight gain was nearly completely arrested in protein-deficient rats compared to control rats. In protein-sufficient rats, chronic alcohol intake decreased body weight gain. Pancreatic weight adjusted with body weight was not different among the 4 groups, but epididymal fat weight adjusted with body weight was decreased in group II compared to group IV. 2. Intraperitoneal glucose tolerance was improved in group I compared to the other groups. Insulin responses to glucose challenge were markedly decreased in group II compared to group IV, but not in group l. 3. Glucose disposal rate during euglycemic clamp test was diminished in group II compared to qroup IV, but there were no differences between group I and group I 3. Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state were not different among the 4 groups. 4. There were no differences of reserved insulin content of whole pancreas adjusted with pancreas weight among the 4 groups. 5. In light microscopic findings of pancreatic islets, sizes of islets, islet cells and nuclei were decreased in protein-deficlent rats compared to control rats. However, the sizes of islet cells and nuclei were further decreased in group II compared to group l. CONCLUSION: These results suggest that impaired insulin secretion and decreased insulin sensitivity due to protein malnutrition can be restored by chronic, moderate amount of alcohol intake, but these beneficial effects may not be appeared in protein-sufficient state. Therefore, the chronic alcohol intake differently influences glucose metabolism according to individual nutritional status, and further studies for the effects of alcohol intake in lean diabetic patients are required to extrapolate these resuits in human.

Relation of Angiotensin Converting Enzyme (ACE) Gene Polymorphism to Insulin Sensitivity and Carotid Atherosclerosis in Female Nondiabetic Offspring of NIDDM Patients.: Jee Young Oh, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang; Korean Diabetes J. 1999;23(6):831-842. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Angiotensin converting enzyme (ACE) gene polymorphism has been known to related to atherosclerotic heart disease such as acute myocardial infarction or left ventricular hypertrophy, diabetic nephropathy or retinopathy, as well as, insulin sensitivity. However, an exact relationship between ACE gene polymorphism and aforementioned diseases have not been fully established. It has been suggested that NIDDM and atherosclerosis may have common pathogenesis since some of NIDDM patients already have atherosclerotic changes at the time of the initial diagnosis. Futhermore, offspring of NIDDM patients are considered as a high risk group for both NIDDM and atherosclerosis, and these two disorders are known to be affected by some common genetic factors. Therefore, in the present study, we planned to investigate, by analyzing female offspring of NIDDM patients (offspring), the relationship of ACE gene polymorphism to insulin resistance and atherosclerosis. METHODS: Fifty-three female offspring of patients with NIDDM were participated in this study, and twenty age-BMI matched normal glucose tolerant subjects without a family history of diabetes were selected as the controls. Based on 75-g oral glucose tolerance test, subjects were divided into normal glucose tolerance (n=42) or impaired glucose tolerance (n=ll). We assessed the patterns of body fat distribution by anthropometric measurement, bioelectric impedence analysis and computed tomogram; insulin sensitivity by minimal model analysis using insulin modified frequently sampled intravenous glucose tolerance test; carotid intima-medial thickness by ultrasonography. We investigated the alleles of the ACE gene by PCR. RESULT: 1. ACE genotypes in offspring were distributed as follows; 39.6% for II, 32.0% for ID, 28.4% for DD 55.7% for I al#lele, 44.3% for D allele. This distribution was not significantly different from those in controls (35.0% for II, 55.0% for ID, 10.0% for DD, 62.5% for I allele, and 37.5% for D allele). 2. There was no significant difference in body mass index (BMI), systolic and diastolic blood pressure, and serum lipid concentrations among three genotypes. However, in the subjects with ID genotype, VSR was significantly increased compared to the subjects with DD genotype (p<0.05). In the subjects with ID genotype, percent body fat, visceral fat area, CIMT were increased, and SI and SG were decreased in comparison to II and DD subjects, although the differences between the two groups did not reached the statistical significance. 3. When the subjects were divided into quartiles of CIMT, the frequency of ID genotype of ACE showed the tendency of increment from the lowest to the highest quartile of CIMT. 4. Multiple regression analysis showed that ACE genotypes was significantly associated with visceral obesity, carotid intima-medial thickening and insulin sensitivity. CONCLUSION: ACE genotypes was not significantly associated with visceral obesity, carotid intima- medial thickening and insulin sensitivity. However, to explore the true associations of ACE gene polymorphism with insulin resistance and ather-osclerosis, we further suggest and recommend prospective studies.

Insulin Secretion, Insulin Sensitivity and Body Fat Distribution Patterns in Patients with Impaired Glucose Tolerance.: Jin Hwa Lee, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang; Korean Diabetes J. 1999;23(5):647-660. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus(DM) is characterized by impaired insulin secretion and decreased insulin sensitivity, and often preceded by impaired glucose tolerance (IGT). To determine the relative importance of impaired insulin secretion and insulin resistance in development of type 2 DM, we evaluated body fat distribution patterns, insulin secretion and sensitivity in patients with IGT. METHODS: Thirty-six patients with IGT and age and weight matched twenty-four control subjects, were recruited from urban diabetes incidence cohort. Fasting serum glucose and insulin were measured. Body fat distribution pattern was assessed by waist to hip ratio (WHR), percent body fat and fat mass measured by bioelectrical impedence analyzer, and visceral to subcutaneous fat ratio (VSR) at the level of umbilicus using the computed tomography. Using insulin modified intravenous glucose tolerance test, insulin sensitivity was measured as minimal model derived sensitivity index (S(I)), and insulin secretion was measured as acute insulin response to glucose (AIR(g)) and beta-cell disposition index (AlR(g) X Sr). RESULT: l) In the patients with IGT, AIR(g)X S(I)(p<0.01) and area under the curve of insulin (AUC(I))(p<0.01) were significantly decreased compared with control subjects and age was greater than control subjects without statistical significance (p=0.17). 2) In the patients with IGT, body fat distribution patterns, indices of insulin secretion and sensitivity were not different according to the presence of family history of DM. AIR, and S(I) were negatively correlated in control subjects (r=-0.38, p=0.08) and the patients with IGT without family history of DM (r=-0.37, p=0.10), but not in the patients with IGT with family history of DM. 3) In the patients with IGT, indices of insulin secretion and sensitivity were not different according to body mass index (BMI). In both obese (BMI>=25 kg/m ) and non-obese (BMI<25 kg/m) patients with IGT, AIR(g)(p<0.05) and AIR(g) X S(I) were significantly decreased compared with control subjects (p<0.01). 4) In control subjects, age (p<0.05) and body fat mass (p<0.05) were significantly associated with AIR(g) X S(I) by multiple regression analysis. In the patients with IGT, body fat mass was significantly associated with AIR(g)(p<0.01) and AUC(I)(p<0.01), and BMI(p<0.01) was significantly associated with S(I). CONCLUSION: In patients with IGT, impaired insulin secretion was more prominent than decreased insulin sensitivity as compared with control subjects regardless of obesity and the presence of family history.

The Effect of Cyclosporine on Insulin Sensitivity in Streptozotocin Induced Diabetic Rats.: Ju Seop Kang, Dong Sun Kim, Chang Beom Lee, Yong Soo Park, Woong Hwan Choi, Tae Wha Kim, Mok Hyun Kim; Korean Diabetes J. 1999;23(2):142-146. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Cyclosporine (CsA), being used as a immunosuppressant is known to have deleterious effects on the liver and kidney, but the harmful effect on glucose tolerance has not been clearly elucidated. This study was undertaken to determine whether the CsA affected peripheral insulin sensitivity in streptozotocin (STZ)-induced diabetic Sprague-Dawley rats. METHODS: After the daily treatment of CsA (10mg/kg, i.p.) for 2 weeks, glucose tolerance tests were carried out by the intraperitoneal administration of glucose alone or in conjunction with insulin (5 U/kg, s.c.). The glucose tolerance and peripheral insulin sensitivity were determined by measuring the deremental area under the time-lasma glucose concentration curve (AUC; mg-min/mL) according to the trapezoidal rule. The plasma glucose levels (mg/dL) were measured by a glucose analyzer at 0, 10, 30, 60, 90 and 120min after glucose load (2 g/kg). The STZ-diabetic rats were divided into thre groups (GLU- as control, INS+GLU- and CsA+INS+GLU-treated group, n 7 in each groups). RESULTS: In STZ-diabetic rats, the AUC 0-120 of the CsA+INS+GLU-treated group was significantly (p<0.01) lower than those of the control group (48.6% of control), but significantly (p<0.03) higher thain those of the INS+GLUtreated group (28.1% of control). CONCLUSIONS: These results suggest that intraperitoneal injection of CsA gives rise to a deterioration of glucose etabolism which is probably due to a decrease of insulin sensitivity of peripheral tissue in STZ-diabetic rats.

Insulin Resistance and Related Factors in the Healthy Young Men.: Seok Won Park, Yoon Sok Chung, Yong Seok Yun, Bong Soo Cha, Young Duk Song, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(4):504-512. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Resistance to insulin-stimulated glucose uptake is present in the majority of patients with obesity, glucose intolerance, hypertension, dyslipidemia, and coronary artery disease. It is known that values for insulin-stimulated glucose uptake(insulin sensitivity) vary widely within individuals with normal glucose tolerance. We investigated the variations in insulin sensitivity and related factors in the nonobese healthy young men. METHODS: Insulin sensitivity was considered as whole body insulin-stimulated glucose uptake rate(M), determined by euglycemic hyperinsulinemic clamp technique in 44 non-obese healthy young men with normal glucose tolerance. Plasma glucose, insulin, and C-peptide concentrations after a standard oral glucose tolerance test and total cholesterol, triglyceride, and HDL-cholesterol levels were measured after 12-hours fasting. The subjects were divided into four quartiles based on the insulin sensitivity (M) and their clinical and biochemical characteristics were compared. RESULTS: Glucose disposal rates (M-values) were ranged from 4.14 to 11.06 mg/kg/min and distributed normally. The plasma glucose levels were not different between quartiles but plasma insulin levels of quartile 1 were significantly higher than the other three quartiles during oral glucose tolerance test. There was a curvilinear relationship between insulin sensitivity and acute insulin response (Ins[o-30]) to oral glucose challenge. There were negative cnrrelations between insulin sensitivity and BMI, percent ideal body weight, WHR, body fat content, fasting insulin level, insulin response area during OGTT, and fasting serum triglyceride level. HDL-cholesterol concentration was positively correlated with insulin sensitivity. In multiple linear regression analysis, body fat content, fasting insulin, and HDL-cholesterol were independent variables, which were related to the insulin sensitivity. CONCLUSION: There were considerable variations in insulin sensitivity in the nonobese healthy young men with normal glucose tolerance and the related independent factors were body fat content, fasting insulin, and HDL-cholesterol cancentrations.

Dehydroepiandrosterone-Sulfate, Sex Hormone Binding Globulin, Body Fat Distribution Pattern and Insulin Resistance in Women.: Young Sun Hong, Jee Young Oh, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang; Korean Diabetes J. 1998;22(3):328-337. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Sex hormone-binding globulin (SHBG) has been known to be associated with obesity, central fat accumulation and insulin resistance and thought to be a indirect marker for androgenicity in women. The relationships between circulating dehydroepiandrosterone(DHEA). dehydroepiandrosterone sulfate(DHEA-S) levels and body fat accumulation are still controversial. We conducted a cross-sectional study to eva]uate the relationships between serum levels of SHBG, DHEA-S, body fat distribution pattern and insulin sensitivity in women. METHODS: We tested 57 women(age 30~65yr; BMI 18.5~32.8kg/m, 45 premenopausal on the 5~10 day of the menstrual cycle, 12 postmenopausal who were not using hormone replacement therapy) with varying degree of glucose tolerance(32 normal glucose tolerance(NGT), 17 impaired glucose tolerance(IGT) and 8 newly diagnosed diabetes). lnsulin sensitivity was measured as minimal model derived sensitivity index(S) using insulin modified IV glucose tolerance test and fasting serum levels of SHBG and DHEA-S were measured by RIA. Body fat distribution pattern was assessed by waist to hip ratio(WHR),% body fat measured by bioelectrical impedance analyzer, subcutaneous fat area(SFA), visceral fat area(VFA) and VFA to SFA ratio(VSR) at the level of umbilicus using the computed tomography. RESULTS: 1) Measured SHBG and DHEA-S levels were not significantly different among subjects with NGT, IGT and diabetes. 2) SHBG was inversely associated with age, BMI, WHR, diastolic blood pressure, VFA, SFA, VSR,% body fat, fasting insulin and positively associated with S, whereas DHEA-S did not show any significant correlation with above variables except diastolic blood pressure. 3) SHBG level was significantly lower(p<0.05) and DHEA-S level was insignificantly lower (p=0.05) in postmenopausal women than in premenopausal women but the significance disappeared after adjustment for age, BMI, WHR and% body fat. 4) BMI was independently and negatively related to S, WHR and fasting insulin to SHBG by multiple regression analysis. CONCLUSION: We confirmed that SHBG was independently associated with central obesity and fasting hyperinsulinemia. However, S was independently associated with BMI only. It suggested that hyperinsulinemia in insulin resistance might cause the decreased level of SHBG even thaugh the directionality of the association was uncertain because of a cross-sectional nature of this study.

Short Insulin Tolerance Test(SITT) for the Determination of in vivo Insulin Sensitivity-A Comparison with Euglycemic Clamp Test.: Seok Won Park, Yong Seok Yun, Churl Woo Ahn, Jae Hyun Nam, Suk Ho Kwon, Min Kyung Song, Seol Hye Han, Bong Soo Cha, Young Duk Son, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(2):199-208. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The euglycemic hyperinsulinemic clamp technique is currently regarded as gold standard for measuring insulin sensitivity, but it requires sophisticated equipment and highly trained personnel. We investigated the reliability of short insulin tolerance test as a simple tesl to measure in vivo insulin sensitivity. METHODS: Short insulin tolerance test(SITT) and euglyeemic hyperinsulinemic clamp test were performed at random order in 14 healthy subjects and 10 abnormal glucose tolerant subjects. The plasma glucose disappearance rate(kitt: %/min) after iv injection of regular insulin(0.1U/kg) was determinecl and compared to insulin sensitivitv indices(M, M/I) of euglycemic hyperinsulinemic clamp test. RESULTS: The mean Kitt value of healthy subjects was 3.50+0.75%/min and that of subjects with abnormal glucose tolerance was 2.56+0.56%/min. Changing sampling time from 15 min to 18~21 min and sampling interval from 3 min to 1.5 min had no influence on Kitt value. Kitt values were reproducible in six subjects, with a CV of 8.8+2.0%. There was a highly significant correlations between the Kitt value derived from SITT and M or M/I derived from euglycemic hyperinsulinemic clamp test. There were no significant adverse effects including hypoglycemic symptom while performing SITT. CONCLUSION: SITT is simple, safe, rapid to perform, and provides reliable index of in vivo insulin sensitivity. It seems particularly suitable for studies involving large series of subjects or including repeated evaluation of insulin sensitivity.

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