OBJECTIVEThe strong relation between type 2 diabetes mellitus and obesity with acanthosis nigricans is widely concerned. This study investigated the pancreatic beta-cell function in obese children with acanthosis nigricans, so as to find out the role of insulin secretion and insulin resistance in obese children with acanthosis nigricans.

METHODSThirty-five obese children with acanthosis nigricans (19 males and 16 females with mean age 12.8 +/- 1.5 years) were enrolled in this study. Thirty-eight obese children (21 boys and 17 girls with mean age 11.9 +/- 2.6 years) and 39 normal children (20 boys and 19 girls with mean age 11.2 +/- 2.2 years) were recruited as obese and normal control groups. The levels of serum fasting insulin, C-peptide, proinsulin and true insulin were measured in all the subjects. The ratios of proinsulin/insulin and proinsulin/C-peptide were calculated. Homeostasis model assessment was applied to assess the status of insulin resistance and basic function of pancreatic beta-cell.

RESULTSThe levels of fasting insulin, C-peptide proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index of obese children with acanthosis nigricans, obese control children and normal control children were: 18.5 (5.0-60.5) pmol/L, 12.4 (6.1-35.8) pmol/L and 5.1 (2.0-32.8) pmol/L; 3.9 (1.3-14.0) microg/L, 2.4 (1.1-4.0) microg/L and 1.1 (1.0-4.2) microg/L; 28.8 (9.9-64.2) pmol/L, 9.5 (2.2-34.5) pmol/L and 4.2 (2.0-16.0) pmol/L; 33.0 (6.2-66.0) pmol/L, 10.6 (4.8-29.4) pmol/L and 4.5 (1.3-30.1) pmol/L; 1.2 (0.4-8.9), 0.9 (0.2-1.9) and 0.8 (0.4-2.0); 6.9 (2.5-36.6), 4.7 (1.2-12.3) and 3.6 (1.2-9.6); 5.0 (0.8-14.1), 2.6 (1.3-8.1) and 1.2(0.4-6.9); 303.3 (52.2-1,163.8), 213.6 (84.6-572.0) and 51.1 (19.1-561.4). The levels of fasting insulin, C-peptide, proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index in obese children with acanthosis nigricans were significantly higher than those in obese children (P < 0.001) and normal children (P < 0.001).

CONCLUSIONObese children with acanthosis nigricans had higher insulin resistance and pancreatic beta-cell dysfunction; acanthosis nigricans may be a skin sign of high risk of type 2 diabetes mellitus.

Acanthosis Nigricans ; complications ; Adolescent ; C-Peptide ; blood ; Child ; Diabetes Mellitus, Type 2 ; etiology ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Islets of Langerhans ; physiopathology ; Male ; Obesity ; complications ; physiopathology ; Proinsulin ; blood

Insulinoma with hyperproinsulinemia and normal serum insulin level is a rare disease. Because of the neuroglycopenic symptoms, the initial diagnosis tends to be made as epilepsy or as psychosis. A 43-year-old man was admitted to our hospital because of recurrent confusional episodes. Symptoms are intermittent and consist of staring, confusion, amnesia, and bizarre behavior. Vital signs during the episode were normal but the serum glucose level was 27 mg/dl. The serum level of insulin during the episode was lower than normal and those of proinsulin and growth hormone were higher than normal. Solitary pancreatic mass was found by abdominal CT, measuring 15 mm in diameter. Pathologic evaluation showed islet cell tumor. This suggests that the serum level of proinsulin should be checked when insulinoma with neuroglycopenic symptom is suspected.
Adenoma, Islet Cell ; Adult ; Amnesia ; Blood Glucose ; Diagnosis ; Epilepsy ; Growth Hormone ; Humans ; Insulin ; Insulinoma* ; Proinsulin ; Psychotic Disorders ; Rare Diseases ; Seizures* ; Tomography, X-Ray Computed ; Vital Signs

BACKGROUND: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. APPROACH: An expert committee compiled evidencebased recommendations for the use of laboratory analysis in patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. A draft of the guidelines was posted on the Internet, and the document was modified in response to comments. The guidelines were reviewed by the joint Evidence-Based Laboratory Medicine Committee of the AACC and the National Academy of Clinical Biochemistry and were accepted after revisions by the Professional Practice Committee and subsequent approval by the Executive Committee of the American Diabetes Association. CONTENT: In addition to the long-standing criteria based on measurement of venous plasma glucose, diabetes can be diagnosed by demonstrating increased hemoglobin A1c (HbA1c) concentrations in the blood. Monitoring of glycemic control is performed by the patients measuring their own plasma or blood glucose with meters and by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.
Autoantibodies ; Biochemistry ; Blood Glucose ; C-Peptide ; Consensus ; Diabetes Mellitus ; Genetic Testing ; Glucose ; Hemoglobin A, Glycosylated ; Hemoglobins ; Humans ; Insulin ; Internet ; Joints ; Plasma ; Professional Practice ; Proinsulin

OBJECTIVETo investigate the difference between serum true insulin (TI) and immunoreactive insulin (IRI) in evaluating islet beta-cell function and insulin resistance.

METHODSThe arginine stimulation test was performed in 141 individuals, including 35 with normal glucose tolerance (NGT) and 106 with type 2 diabetes (T2DM). Plasma glucose (PG), TI, IRI and proinsulin (PI) levels were measured; the incremental value of TI/PG, (TI+PI)/PG and IRI/PG (delta TI/PG, delta(TI+PI)/PG and deltaIRI/PG) and the area under curve of TI/PG, (TI+PI)/PG and IRI/PG (AUC [TI/PG], AUC[(TI+PI)/PG] and AUC [IRI/PG]) after arginine stimulation were calculated to evaluate beta-cell function.

RESULTThere were positive correlations of delta TI/PG with delta (TI+PI)/PG and delta IRI/PG in both NGT and T2DM patients (r=0.68 - 0.99, P<0.01). The similar correlations of AUC [TI/PG] with AUC [(TI+PI)/PG] and AUC [IRI/PG] were also shown (r=0.62 - 0.99, P<0.01). delta TI/PG was correlated with AUC [TI/PG] in two groups (NGT r=0.96, T2DM r=0.82, P<0.01). HOMA-IRTI, HOMA-IR(TI+PI) and HOMA-IRIRI in T2DM were higher than those in NGT (P<0.01). After arginine stimulation T2DM subjects mainly presented insulin resistance and decreased insulin secretion.

CONCLUSIONThe determination of TI may be more accurate than IRI in evaluating beta-cell function and insulin resistance.

Adult ; Aged ; Arginine ; pharmacology ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; Female ; Glucose Tolerance Test ; Humans ; Insulin ; blood ; immunology ; Insulin Resistance ; Insulin-Secreting Cells ; physiology ; Male ; Middle Aged ; Proinsulin ; blood

BACKGROUND: Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. METHODS: We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also investigated the relationship between serum insulin, proinsulin and proinsulin/insulin ratio and several biochemical markers which represent insulin resistance or beta cell function. RESULTS: Insulin, proinsulin and proinsulin/insulin ratio were significantly higher in type 2 DM than control(p < 0.001). In diabetic patients, total insulin level was correlated with urinary albumin excretion rates(r = 0.224, p = 0.025) and body mass index(r = 0.269, p = 0.014). Proinsulin level was correlated with fasting C-peptide(r = 0.43, p = 0.002), postprandial 2 hour blood glucose(r = 0.213, p = 0.05) and triglyceride(r = 0.28, p = 0.022). Proinsulin/insulin ratio was positively correlated with fasting C-peptide(r = 0.236, p = 0.031), fasting blood glucose (r = 0.264, p = 0.015), postprandial 2 hour blood glucose(r = 0.277, p = 0.001) and triglyceride(r = 0.428, p < 0.001). In control subjects, insulin level was correlated with triglyceride(r = 0.366, p = 0.002). Proinsulin/insulin ratio was correlated with age(r = 0.241, p = 0.044). CONCLUSION: The serum levels of insulin and proinsulin seem to be associated with several markers of insulin resistance. Whereas proinsulin/insulin ratio might represent beta cell function rather than insulin resistance. But more studies are needed to clarify the mechanisms of elevated proinsulin/insulin ratio in type 2 DM.
Aged ; Diabetes Mellitus, Non-Insulin-Dependent/etiology ; Diabetes Mellitus, Non-Insulin-Dependent/blood* ; Female ; Human ; Insulin/blood* ; Insulin Resistance* ; Islets of Langerhans/physiopathology* ; Male ; Middle Age ; Proinsulin/blood* ; Sulfonylurea Compounds/pharmacology

BACKGROUND: Leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the leptin is increased in obese adults even in children. This study investigated whether the serum leptin in cord blood was related to babys birth weight and metabolic parameters. METHODS: 71 pairs of singleton pregnancy babies and their mother were studied. Babies are classified in LGA (large for gestational age), AGA (appropriate for gestational age), SGA (small for gestational age) three groups. After delivery, cord blood and maternal venous blood samples were drawn. We measured the plasma leptin, insulin-like growth factor (IGF)-1, insulin and proinsulin in cord and maternal serum. RESULTS: The concentration of leptin from cord blood was increased in LGA babies and decreased in SGA babies compued with the level in AGA babies. There was positive correlatian (r=0.55, p<0.01) between the plasma leptin level in cord and birth weight. There were positive correlatian between both the plasma proinsulin (r=0.37, p<0.01) and IGF-1 (r=0.32, p<0.01) and birth weight, too. But there was no difference between female and male baby's cord blood leptin level. In multiple regression analysis, cord blood leptin level was found independent factor related to birth weight ( p=0.001) CONCLUDION : The plasma leptin, proinsulin and IGF-1 is correlates to the birth weight. These data provide evidence that leptin and proinsulin are highly related to the nutritional status already during the fetal periods, and effect on the intrauterine fetal growth.
Adipose Tissue ; Adult ; Birth Weight* ; Body Weight ; Child ; Female ; Fetal Blood* ; Fetal Development ; Humans ; Insulin ; Insulin-Like Growth Factor I ; Leptin* ; Male ; Mothers ; Nutritional Status ; Parturition* ; Plasma ; Pregnancy ; Proinsulin

BACKGROUND: It is well known that non-alcoholic fatty liver disease is associated with metabolic syndrome such as obesity, type II diabetes mellitus, dyslipidemia. Non-alcoholic fatty liver disease is frequently found in non-obese adults, but the meaning of it is unknown. So we studied the association of non-alcoholic fatty liver disease in non-obese adults and metabolic abnormalities. METHODS: We examined 779 Korean adults above 30 years old (274 men, 505 women) participating in medical check-up in Health Promotion Center. Hepatitis B and C serologies were negative, and average weekly alcohol intake was or=25 kg/m2, n=348) group (65.5 vs 32.3%, p<0.05). Compared with obese group, waist circumference, waist hip ratio, body fat, impaired fasting serum glucose, total cholesterol, HDL-cholesterol, total cholesterol to HDL-cholesterol ratio, fasting insulin, proinsulin, HOMA-IR and HOMA-beta were significantly different in non-obese, non-alcoholic fatty liver group. After multiple regression analysis, waist circumference was associated with non-alcoholic fatty liver disease in non-obese individuals. Odd ratios of insulin resistance in non-obese, non-alcoholic fatty liver group were 5.8 (CI: 3.1~10.9). CONCLUSION: The frequency of non-alcoholic fatty liver disease was very high in non-obese adults and well associated with central obesity and insulin resistance.
Adipose Tissue ; Adult* ; Blood Glucose ; Body Mass Index ; Cholesterol ; Diabetes Mellitus ; Dyslipidemias ; Fasting ; Fatty Liver* ; Female ; Health Promotion ; Hepatitis B ; Humans ; Insulin ; Insulin Resistance ; Liver ; Male ; Obesity ; Obesity, Abdominal ; Physical Examination ; Proinsulin ; Ultrasonography ; Waist Circumference ; Waist-Hip Ratio

The insulin complement with gene therapy has been used as an experimental treatment for insulin dependent diabetes (IDDM). In the present study, we constructed naked plasmid DNA vector encoding recombinant human preproinsulin gene (pCMV-IN), and injected the plasmids (100 microg/mouse) intramuscularly combined with electroporation, to achieve the in vivo transfer of insulin gene in streptozotocin (STZ)-induced diabetic C57 mice. The expression of vector-derived insulin mRNA was detected with RT-PCR in transfected local skeletal muscles. The plasma insulin was elevated significantly in pCMV-IN injected diabetic C57 mice, which was complemented to the level similar to the intact normal control. The protein expression lasted for at least 35 days after the plasmid injection. Gene therapy with pCMV-IN plasmids considerably decreased the blood glucose level in STZ-induced diabetic mice from d 7 to d 35 by about 6 mmol/L. The gene therapy also reduced the mortality of severe diabetic mice significantly from 100% to 37% at the 6th week. Our results indicate that the direct intramuscular injection of naked plasmids encoding human preproinsulin gene achieves the effective expression of insulin. The restoration of insulin decreases blood glucose and increases the survival in severe diabetic mice. The gene therapy might be provided as a practical therapeutic approach to IDDM.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; blood ; therapy ; Diabetes Mellitus, Type 1 ; blood ; therapy ; Electroporation ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Genetic Vectors ; Injections, Intramuscular ; Insulin ; Male ; Mice ; Mice, Inbred C57BL ; Plasmids ; genetics ; Proinsulin ; genetics ; therapeutic use ; Protein Precursors ; genetics ; therapeutic use

BACKGROUND : This study was initiated to evaluate the prevalence of metabolic syndrome and its components as risk factors for cardiovascular disease according to insulin resistance in the Korean adult population. METHODS : This study was conducted as a branch of the Korean Metabolic Syndrome (KMS) Study: 1,091 individuals aged 30 79 years participating in medical check-up in Korea Association of Health (KAH) were included in this study. We checked fasting blood sugar, fasting insulin, proinsulin, lipid profiles (total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol), body mass index, waist circumference, blood pressure, carotid intima-media thickness (IMT) and abdominal ultrasonography. We divided all of the examinees into three groups (insulin sensitive, intermediate, resistant tertiles) according to their degree of insulin resistance and correlated this with the prevalence of metabolic syndrome. RESULTS : The relative risk of metabolic syndrome was 84.1-fold higher in the insulin resistant tertile group compared to the insulin sensitive tertile group. Diabetes mellitus or impaired fasting glucose (IFG) was 10.2-fold; hypertension, 1.8-fold; dyslipidemia, 2.8-fold; hypercholesterolemia, 2.5-fold; fatty liver, 3.0-fold. Abdominal obesity rather than general obesity was more contributory to insulin resistance. CONCLUSION : Although this is a cross-sectional study, we can show that insulin resistance is one of the most-striking risk factors in metabolic syndrome and can be used as a predictor of cardiovascular diseases. Furthermore, we should monitor the healthy insulin-resistant population to prevent ongoing cardiovascular diseases. More prolonged data should be gained to refine the correlations of insulin resistance to metabolic syndrome.
Adult ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Carotid Intima-Media Thickness ; Cholesterol ; Cross-Sectional Studies ; Diabetes Mellitus ; Dyslipidemias ; Fasting ; Fatty Liver ; Glucose ; Humans ; Hypercholesterolemia ; Hypertension ; Insulin Resistance* ; Insulin* ; Korea ; Obesity ; Obesity, Abdominal ; Prevalence ; Proinsulin ; Risk Factors ; Triglycerides ; Ultrasonography ; Waist Circumference

The aim of this study is to investigate the therapeutic effect of RegIII-proinsulin-pBudCE4.1 plasmid on streptozotocin (STZ)-induced type 1 diabetes mellitus and its underlying mechanisms. The model of type 1 diabetes mellitus was established by intraperitoneal injections of STZ (40 mg kg(-1)) to Balb/c mice for five consecutive days. Then, ten type 1 diabetic mice were intramuscularly injected with 100 microg RegIII-proinsulin-pBudCE4.1 plasmid for 4 weeks (one time/week) and the blood glucose levels were monitored every week; whereas another ten diabetic mice served as negative control group were injected with pBudCE4.1 vector at the same dose. Normal control and model control mice were treated with normal saline at identical volume under the same way. Western blotting, MTT assay, ELISA, HE staining and Tunel assay were applied to explore the underlying mechanisms. Results showed that RegIII-proinsulin-pBudCE4.1 plasmid ameliorated the hyperglycemia symptoms in diabetic mouse remarkably. It induced an immunological tolerance state in type 1 diabetic mice by inhibiting the proliferation of splenic lymphocytes and recovering Th1/Th2 balance evidenced by MTT and ELISA analysis. Furthermore, it elevated insulin concentration in the serum of type 1 diabetic mice and promoted the regeneration of beta cells supported by the results of HE staining and Tunel assay. In conclusion, RegIII-proinsulin-pBudCE4.1 plasmid possesses powerful anti-diabetic ability, which may be involved in the inducing of immunological tolerance and enhancing beta cells recovery.
Animals ; Apoptosis ; Blood Glucose ; metabolism ; Cell Proliferation ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; therapy ; Diabetes Mellitus, Type 1 ; chemically induced ; metabolism ; pathology ; therapy ; Genetic Therapy ; Hyperglycemia ; therapy ; Injections, Intramuscular ; Insulin ; blood ; Islets of Langerhans ; cytology ; Male ; Mice ; Mice, Inbred BALB C ; Plasmids ; Proinsulin ; genetics ; metabolism ; therapeutic use ; Proteins ; genetics ; metabolism ; therapeutic use ; Streptozocin ; T-Lymphocytes ; cytology ; Th1-Th2 Balance