Diabetes & Metabolism Journal

Original Articles

Plasma Proinsulin Secretion in Impaired Glucose Tolerance and Newly Diagnosed Type 2 Diabetes Mellitus.: Byoung Ho Kong, Seung Jin Choi, Jae Tack Kim, Yeon Shang Oh, Soon Hyun Shinn; Korean Diabetes J. 2000;24(4):467-475. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus is characterized beta cell dysfunction and insulin resistance but the relative roles of the two factors are different in various ethnic groups. The changes in plasma proinsulin levels is thought to be a marker for the beta-cell dysfunction. To study the role of beta cell dysfunction in the pathogenesis of type 2 diabetes mellitus we compared the concentrations of plasma insulin, C-peptide and proinsulin among the control group, impaired glucose tolerance (IGT) group and newly diagnosed Type 2 Diabetes Mellitus (DM) group during the oral glucose tolerance test. METHODS: In 47 newly diagnosed patients with type 2 DM, 9 IGT and 13 controls the 75g oral glucose tolerance test (OGTT) were performed and samples were analyzed for glucose, insulin, C-peptide and proinsulin. RESULTS: 1) In IGT group plasma insulin, C-peptide and proinsulin concentrations were increased markedly during OGTT but were blunted in type 2 diabetes group. 2) The basal plasma proinsulin level was 7.7+/-4.4 pmol/L in control group, 15.2+/-6.9 pmol/L (p<0.005) in IGT group, and 16.9+/-8.3 pmol/L (p<0.005) in type 2 DM group, and the proinsulin levels at 60 min, 90 min, 120 min during OGTT were significantly elevated in IGT group than those of control group. 3) The plasma proinsulin/insulin ratio were significantly increased in IGT group and type 2 DM group at basal and 30 min during OGTT. 4) The proinsulin response areas were significantly increased in IGT group (110.7+/- 13.1 pmol/L/hr, p=0.048) than those of control group (73.6+/-5.1 pmo l/L/hr) and type 2 DM group (80.5+/-5.9 pmol/L/hr). CONCLUSION: Beta cell secretory defects such as proinsulin secretion were present in impaired glucose tolerance and the changes of insulin secretory function might have a role in the pathogenesis of type 2 DM.

Evaluation of 25% and 50% -75 gm Oral Glucose Tolerance Test - Animal and Clinical Pilot Study: Emphasis on Glucose Kinetics and Preference Evaluation.: Nam Han Cho, Eun Gyoung Hong; Korean Diabetes J. 2000;24(3):385-392. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Oral glucose tolerance test to diagnose diabetes was first introduced by Jarney and Isaacson in 1918. This method was advocated because of its diagnostic accuracy and also provides the two hours glucose changing pattern. Twenty-five percent (296 mL) glucose solution has been used as the standard diagnostic method in Korea. However, large volume of the solution frequently cause vomiting during the tests. Thus, 50% solution (150 mL) was recently introduced, but the potential difficulty of gastric emptying caused by its hyperosmolarity, and degree of diagnostic accuracy was questioned. Therefore, in this study, we evaluated two type of solutions by comparing the followings in both an animal and human models: (1) glucose changing pattern during the two hour oral glucose tolerance test, (2) Preference evaluation in human model. METHODS: Fifteen male Sprague-Dawley rats and 15 human subjects underwent 2 hours OGTT after 10~14 hours fasting. Two grams glucose per kg body weight was feed to the SD rat. In human, 75 gm glucose in 296 mL (25%) and 150 mL (50%) glucose solution was ingested at two different time, but testing was done within 24 hours a part. Five blood samples (fasting, 30, 60, 90, and 120 minutes) were collected and separated for serum. Glucose was assayed using YSI 2300-STAT (Yellow Springs Instrument Co., Ohio, USA) by glucose oxidase method. RESULTS: In animal study, despite the lower fasting glucose level, 30, 60 and 120 minutes glucose level was higher in 50% solution when compared to the 25% but the mean values were not statistically different. The glucose area under the curve (GAUC) in 50% was higher than 25% but not statistically different. The peak glucose level was observed at 60 minutes in both solutions. In human study, although mean values were not statistically different, all glucose values except 30 minutes were higher in 50% solution. Furthermore, GAUC was not statistically different between the two solutions. In preference test, the study subjects significantly (p<0.05) preferred the 50% solution as more favorable amount for the test. No differences in the tolerable level of sweetness, level of thirsty after ingestion, nausea, vomiting, head and stomachache was observed. CONCLUSION: In this study, we found that the gastro-intestinal glucose kinetics of the 25% and 50% glucose solution used during the OGTT was very similar in both an animal and human model. Furthermore, the preference evaluation showed favorable results in 50% solution. The use of 50% solution reconcile vomiting problem during the test but the same diagnostic accuracy was preserved. Therefore, 50% solution merits its scientific value as the diagnostic solution, and hope to contribute to favor the OGTT for diagnosis of diabetes mellitus in the future.

Serum Proinsulin Responses during Oral Glucose Tolerance Test in patients with Non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Yong Seong Kim, In Young Hyun, In Ho Kwak; Korean Diabetes J. 1997;21(4):356-364. Published online January 1, 2001

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Abstract PDF: BACKGROUND
When insulin is secreted from the pancreas, a small amount of proinsulin is also secreted at the same time. Pancreatic beta cell may release immature granules richer in proinsulin contents as well as mature granules in the over-stirnulated state. The significance of hyperproinsulinemia was recently reevaluated in the pathogenesis of non-insulin dependent diabetes mellitus(NIDDM). We studied proinsulin response at fasting and oral glucose tolerance test(OGTT) in NIDDM with a simple and sensitive human proinsulin radioimmunoassay system. METHODS: 22 new onset non-obese NIDDM patients and 11 matched healthy controls were selected for the study. The NIDDM group was divided into 3 groups(group 1; 7.8, group 2; 7.8~11, group 3; 11.0 mmol/L) according to the fasting plasma glucose level. After an overnight fast, a 75 g OGTT was performed and samples were analyzed with proinsulin and specific human insulin radioimmunoassay kits. RESULTS: The basal serum proinsulin level was reported as 9.29+/-4.19 pmol/L in normal control and as 18.09+/-9.32 pmol/L(p=0.04, compared with control) in diabetic group. The values in NIDDM group 1 and 2(18.07+/-9.D2; p=0.04, 21.60+/-6.98; p=0.03) were higher than in control. The molar ratia of the basal proinsulin to total insulin were also increased in NIDDM group 1 and 2(0.24, 0.28) than in control subjmts(0.13, p=0.03). The basal proinsulin and proineulin/total insulin ratio were highest in the group 2(p 0,05, than group 3). During oral glucose loading, the proinsulin response increased more slowly than total insulin response. The proinsulin and proinsulin/ total insulin ratio during oral glucose loading were higher in NIDDM group 1 and group 2 than cantrols. CONCLUSION: The basal proinsulin level in diabetic group was higher than in normal control. The proinsulin responses during oral glucose loading were higher in diabetic group 1 and 2 than controls. The proinlulin response increased more slowly than total insulin response during oral glucose loading. So we conclude that the proinsulin secretion frorn pancreatic beta cell is impaired in diabetic group. The mechanism about the metabolic pathway of the proinsulin secretion should be studied more.

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