- Serum Proinsulin, Proinsulin/Total Insulin Ratio and Insulin Resistance in Elderly-onset Type 2 Diabetes.
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Yoon Ju Oh, Young Ju Park, Young Wan Kim, Sung Ki Kim, Seong Bin Hong, Yoe Joo Kim, Mi Rim Kim, Moon Suk Nam, Yong Seong Kim
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Korean Diabetes J. 2001;25(2):113-124. Published online April 1, 2001
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- BACKGROUND
It is well known that the concentration of serum proinsulin and the ratio of proinsulin/total insulin (P/I) are elevated in type 2 diabetes. Proinsulin is produced by the ribosome in pancreatic beta cells, undergoes maturation in Golgi body and exists in the form of secretory granules. Immature granules possess disproportionately large amount of proinsulin. When there is increased demand of insulin caused by diabetes, higher level of proinsulin is secreted from immature granules of dysfunctioning beta cells. Thus, the elevated concentration of proinsulin and the increased ratio of P/I are considered to be the markers of pancreatic dysfunction and predictors for the future development of diabetes. The elderly-onset type 2 diabetes is also thought to develop due to both dysfunction of insulin secretion by impaired beta cell with aging and increased insulin resistance in peripheral tissue due to less muscle mass and more fat. However, it is still controversial as to which mechanism is predominant in the development of type 2 diabetes. METHODS: We measured the levels of fasting blood glucose, serum proinsulin and specific human insulin by using radioimmunoassay kit, and calculated the P/I ratio and insulin sensitivity index in normal adults (40or=60, n=35) and also in the newly-diagnosed elderly type 2 diabetes (age>or=60, n=24). RESULTS: The concentration of serum proinsulin and the ratio of P/I in normal adults over age 40 were 7.70+/-6.08 pmol/L and 0.13+/-0.10, respectively. The concentration of proinsulin in the normal adult, normal elderly and elderly diabetes group were 6.50+/-3.71, 11.17+/-8.30 and 16.75+/-11.68 pmol/L. The differences among three groups were statistically significant (p= 0.0001). The P/I ratios for each of the three groups were 0.11+/-0.05, 0.17+/-0.12 and 0.16+/-0.08 (p=0.0004). P/I ratios in the elderly control and elderly diabetes were higher than that of the normal adult group. Insulin sensitivity index (ISI, 10,000/(basal glucose X basal insulin)) of elderly diabetes (1.19+/-0.89) was lower when compared with the indices of other groups (40or=60 control; 2.27+/-1.11, p=0.0001). CONCLUSION: Although the age-related reduction of pancreatic insulin secretory function attributes to the pathogenesis of old-age onset type 2 diabetes, it appears that the decreased insulin sensitivity may serve as more important factor in the development of the disease.
- Role of Nitric Oxide on the Insulin Secretion of Rat Pancreas.
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Moon Suk Nam, Sung Ki Kim, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Yong Seong Kim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 1999;23(6):748-756. Published online January 1, 2001
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- BACKGROUND
Diabetes mellitus could occur when insulin secretion of pancreas is inadequate in response to blood glucose. The mechanisms on failure of pancreatic beta cell are still not known. Several recent experiments have reported that nitric oxide (NO) may be considered as a modulator of insulin secretion and impairment associated with the beta cell. The present study was purposed to investigate the role of nitric oxide on the secretion of insulin of rat pancreas in vivo and in vitro. METHODS: The plasma insulin and glucose were measured after intravenous injection of nitric oxide synthase (NOS) inhibitor (NG-nitro-L-arginine methyl. ester, L-NAME) in male rat. Insulin release was determmed during stimulation of NOS inhibitor and nitric oxide donor (hydroxylamine) in the isolated pancreatic islets. RESULT: 1. The insulin secretory response with L-arginine stimulation after injection of NOS inhibitor (L-NAME) in rat was increased resulting in mild hypoglycemia which recovered promptly. This showed that NO were related with L-arginine induced insulin secretion. 2. After isolation of pancreatic islet, 11,0 mM glucose induced insulin release was increased in culture media and L-arginine (1.0 mM) induced insulin release was also increased compared with control (6.72+/-0.66 vs. 3.48+/-0.42 prnol/islet/hour, p<0.05). 3. L-arginine induced insulin release was increased with L-NAME in the isolated rat pancreatic islets (12.5+/-1.38 vs, 7.23+/-0.93 ng/islet/ hour, p<0.05). 4. Glucose induced insulin release was progressively inhibited by NO donor hydroxylamine in the isolated rat pancreas islet (6.72+/-0.75 vs. 2.46+/-0.60 pmol/islet/hour p<0.05). CONCLUSION: These results strongly suggest that nitric oxide is a negative modulator of insulin release in normal rats induced by the nutrient secretagogues L-arginine and glucose in vivo and in vitro. Further investigation on the mechanism of nitric oxide in insulin secretory pathway will be necessary.
- Clinical Application of Electrogastrography in Type 2 Diabetic Gastroparesis.
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Seong Bin Hong, Moon Suk Nam, Yoon Juo Oh, Sung Ki Kim, Yoe Joo Kim, Pum Soo Kim, Mi Rim Kim, Yong Seong Kim, Young Soo Kim
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Korean Diabetes J. 1999;23(5):695-701. Published online January 1, 2001
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Electrogastrography (EGG) enables the cutaneous measurement of gastric electric activity. Abnormal gastric slow wave frequencies have been observed in diabetic gastroparesis. The aim of this study was to know the clinical application of EGG, and to determine the relationship between gastric myoelectrical activity and gastric emptying time (GET) in patients with type 2 diabetes mellitus. METHODS: This study included 26 type 2 diabetic patients (11 men, 15 women, mean age 53+/-10 years, disease duration 10.5+/-6.5 years). They were given solid and liquid diet with 1 mCi (99m)Tc DTPA for measuring GET (Tl/2). They were divided into normal GET group (Tl(2 < 60 minutes) and delayed GET group (Tl/2 > 60 minutes). Gastric myoelec-trical activity was recorded by cutaneous EGG. EGG was recorded for 30 minutes in fasting state and 30 minutes in post-prandial state with same test meal. Several EGG variables including percentages of dominant frequency in the normal range (2 cycle per minute, cpm), bradygastria (0.5~2 cpm), tachygastria (4~9cpm), postprandial to preprandial power ratio, and dominant frequency instability coefficient (DFIC) were calculated by fast Fourier transformation. Result: Autonomic nerve function test showed no difference between normal GET group and delayed GET group. EGG values in delayed group did not differ from data in normal group. There were no correlation between b1ood glucose level and GET. In fasting, normal slow wave (r=-0.50, p<0,05) and bradygastria (r=0.50, p<0.05) were correlated with fasting blood glucose. And in postprandial state, normal slow wave (r=0.47, p<0.05) and bradygastria (r=0.84, p<0.05) were correlated significantly with fasting blood glucose. EGG parameters did not correlated with GET CONCLUSION : EGG may be influenced by blood glucose level, but seems to be less valuable for assessment of gastroparesis in Korean type 2 diabetes mellitus, according to our investigation.
- Insulin Secretory Dysfunction in the Patients with Untreated Hyperthyroidism.
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Moon Suk Nam, Seung Yong Shin, Young Wan Kim, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Won Sick Choe, Yong Seong Kim
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Korean Diabetes J. 1998;22(3):320-327. Published online January 1, 2001
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Abnormal glucose metabolism with impaired glucose tolerance has been documented in patients with thyrotoxicosis, but the pathogenesis is not fully understood. Therefore, the aim of the present study was to study the secretory dysfunction of pancreatic 9-cell and to confirm hyperinsulinemia and hyperproinsulinemia during oral glucose tolerance test(OGTT) in patients with thyrotoxicosis. METHODS: After an overnight fast, 75 g OGTT was performed in 10 patients with hyperthyroidism and in 10 healthy control subjects matched for age, sex and hody mass index. Plasma insulin(immuno-reactive insulin, IRI), C-peptide, proinsulin levels were measured by radioimmunoassay. RESULTS: Fasting plasma glucose, insulin and C-peptide levels were similar in the two groups, but plasma proinsulin level was increased in patients with hyperthyroidism(p<0.05). A twofold rise of plasma proinsulin and the proinsulin/insulin ratio was also found in patients with hyperthyroidism during OGTT. The molar ratio of C-peptide and insulin(IRI) was similar in the two groups. CONCLUSION: Hyperinsulinemia and hyperproinsulinemia were found in patients with hyperthyroidism compared with controls. Disproportionally increased proinsulin level suggested a pancreatic secretory dysfunction in the patients with hyperthyroidism.
- Comparison of the New Diagnostic Criteria for Diabetes Mellitus Recommended by the Expert Committee of the American Diabetes Association with the Criteria by the NDDG or WHO in Koreans with Fasting Plasma Glucose between 110 and 139 mg / dL.
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Yeo Joo Kim, Moon Suk Nam, Mi Rim Kim, Yong Seong Kim, Kwan Woo Lee, Hyeon Man Kim, Choon Hee Chung, Su Youn Nam, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Sam Kweon, Yong Wook Cho, Kap Bum Huh
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Korean Diabetes J. 1998;22(2):209-217. Published online January 1, 2001
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The current diagnostic criteria for diabetes mellitus announced by National Diabetes Data Group(NDDG) in 1979 were revised by Expert Committee of World Health Organization(WHO) in both 1980 and 1985. However, according to advancement in the knowledge of the etiology and pathogenesis of diabetes mellitus, the International Expert Committee working under the sponsorship of the American Diabetes Association(ADA) decided to adopt the resolution proposing that the criteria of fasting glucose level applied to diagnosis of diabetes mellitus should be lowered at the 57 ADA conference held in Boston, USA in June 1997(97 ADA). Hereupon, by comparing the diagnostic criteria of the former (NDDG/WHO) with the later, the authors have examined the usefulness of new diaignostic criteria, 97 ADA. METHOD: We collected the data from 13 university hospitals in Korea which contain the results of 75 gram oral glucose tolerance test(OGTT) for 532 Kareans between 110 and 139 mg/dL in fasting plasma glucose. We have then evaluated the results by classifying and comparing them in accordance with the criteria of NDDG/WHO and 97 ADA, respectively. RESULTS: 1. The number which tested for oral glucose tolerance was 532 and the majority of tests have been carried out between 110 and 119 mg/dL in fasting plasma glucose. 2. When we have classified the same results of OGTT by respective diagnostic criteria of NDDG/ WHO and 97 ADA, the NDDG/WHO have diagnosed 50.4%(268/532) of the total number of people as diabetes mellitus, while the '97 ADA has shown that only 33.1%(176/532) of it corresponded to the same diagnosis. On the other hand, the diagnosis rate of impaired fasting glucose(IFG) or impaired glucose tolerance(IGT) has shown 28.8~ 31.8%(NDDG/ WHO) and 66.9%(97 ADA), respectively. 3. Following the diagnostic criteria of the 97 ADA, we have separated the results into two groups which were above and below 126 mg/dL in fasting glucose. In addition, when we have again classified two groups by the criteria of the NDDG/WHO, the group above 126mg/dL in fasting glucose, which was all diagnosed as diabetes mellitus in 97 ADA has represented a ratio of 72.2%(127/176) in same diagnosis. However, within the group below 126mg/ dL, in fasting glucose being classitied as IFG in the 97 ADA, its diagnosis rate of diabetes mellitus has also shown 39.7%(141/356) applying to the criteria of the NDDG/WHO. CONCLUSION: The criteria of the 97 ADA can simply make a diagnosis of diabetes mellitus with fasting plasma glucose and additionally fmd out the IFG whose rate is 17.9 20% regarded as a normal condition by NDDG/WHO, whereas the existing criteria of the NDDG/WHO have to carry out the OGTT which is difficult in clinics. However, since among the patients ot 50.4% diagnosed as diabetes mellitus by NDDG/WHO, the 97 ADA classifies 17.3% of them as IFG, it is regarded that the need of OGTT for the diagnosis of diabetes mellitus can not be passed over in the future.
- Serum Proinsulin Responses during Oral Glucose Tolerance Test in patients with Non-insulin Dependent Diabetes Mellitus.
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Moon Suk Nam, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Yong Seong Kim, In Young Hyun, In Ho Kwak
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Korean Diabetes J. 1997;21(4):356-364. Published online January 1, 2001
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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.
- A follow-up study of diabetic retinopathy by fundus photography in diabetic patients.
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Choon Hee Chung, Kwang Jin Ahn, Young Duk Song, Mi Rim Kim, Kawn Woo Lee, Seung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Seung Chul Lee, Oh Woong Kwon, Yong Wook Cho
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Korean Diabetes J. 1991;15(1):91-101. Published online January 1, 2001
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- No abstract available.
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