Changes of plasma fibroblast growth factor-21 (FGF-21) in oral glucose tolerance test and effects of metformin on FGF-21 levels in type 2 diabetes mellitus.

INTRODUCTION: The objectives of our study were to investigate whether fibroblast growth factor-21 (FGF-21) is involved in short-term regulation of glucose and the change of FGF-21 after metformin use in diabetic subjects. MATERIAL AND METHODS: 43 subjects were recruited in the study, including 27 new-onset type 2 diabetes patients (nT2DM). A 75 g oral glucose tolerance test (OGTT) was administered to them. Blood samples were taken at 0, 60 ,120 and 180 minute of OGTT. nT2DM subjects were invited for further investigation, metformin was administered in a dose of 1.0 g every day for 1 week. RESULTS: Plasma FGF-21 changed significantly in the nT2DM group during the OGTT administration but not in the control group. No gender differences were observed at different time points in FGF-21 levels (p 〈 0.05). Administration of metformin for nT2DM resulted in a significant decrease in both glucose and FGF-21 at all OGTT times and in insulin at 60 min and 180 min, indicative of a decrease in HOMA-IR. CONCLUSION: FGF-21 does not seem to be involved in short-term regulation of glycaemia in human subjects, and the change in OGTT delayed in T2DM. FGF-21 may participate in the processing of metformin, improving glucose and insulin sensitivity.

Frequent reoccurrence of hypoglycemia in a type 2 diabetic patient with insulin antibodies.

BACKGROUND: Insulin antibody (IAb) may be produced in patients receiving long-term, animal-derived insulin, leading to insulin resistance or hypoglycemia. There have been very few reports of hypoglycemia caused by IAb in patients taking recombinant human insulin. CASE REPORT: We report the case of an 82-year-old male patient with type 2 diabetes mellitus who suffered repeated episodes of severe hypoglycemia-related symptoms (including coma) prior to admission. The patient had been taking Novolin 30R, a premixed human insulin. The patient's IAb level was markedly elevated, and hypoglycemia caused by recombinant human insulin treatment-induced IAb production was diagnosed. Acarbose and metformin were prescribed, and the patient recovered uneventfully. The patient ceased taking these medications, and he was subsequently treated with recombinant human insulin to combat hyperglycemia. This was followed by reoccurrence of hypoglycemic coma. The patient was advised to avoid taking recombinant human insulin for the rest of his life and to control hyperglycemia with acarbose and metformin. CONCLUSIONS: Although rare, hypoglycemia caused by recombinant human insulin-induced IAb production should be considered in patients with type 2 diabetes who experience repeated episodes of hypoglycemia.

[Plasma fibroblast growth factor-21 and abdominal obesity].

OBJECTIVE: To investigate the association of plasma fibroblast growth factor-21 (FGF-21) with abdominal obesity and other metabolic indicators. METHODS: Sixty one people with abdominal obesity and 113 healthy controls were recruited. The stature, avoirdupois, waist circumference and blood pressure of the participants were measured. Serum lipid, glucose, insulin and plasma FGF-21 levels of those participants were also determined. RESULTS: 1) The participants with abdominal obesity had significantly higher FGF-21 levels than the healthy controls [(1.91 +/- 0.40) ng/mL vs. (1.75 +/- 0.45) ng/mL, P = 0.020]. 2) Plasma FGF-21 levels were positively associated with BMI (r = 0.24, P = 0.001), waist circumference (r = 0.16, P = 0.033), body fat contents (r = 0.24, P = 0.001), and triglycerides (r = 0.16, P = 0.036) after adjustment for age and sex. The multiple liner regression analysis identified BMI, waist circumference, body fat contents, and triglycerides as factors associated with FGF-21 (P < 0.05). 3) Plasma FGF-21 levels were found to be independently associated with abdominal obesity (OR = 2.413, 95% CI 1.115-5.221, P = 0.025). CONCLUSION: FGF-21 is an independent risk factor for abdominal obesity. It is perhaps an important factor in the occurrence and development of abdominal obesity.

[Protective effect of fibroblast growth factors-21 and rosiglitazone sodium on palmitic acid-induced apoptosis in HIT-T15 cells].

OBJECTIVE: To investigate the protective effect of fibroblast growth factors-21 (FGF-21) and rosiglitazone sodium (RO) on palmitic acid-induced apoptosis in HIT-T15 cells. METHODS: (1) HIT-T15 cells were treated with 0.25 mmol/L, 0.50 mmol/L and 1.00 mol/L of palmitic acid for 24 hours. (2) FGF-21 [12.50 nmol/L (A), 25.00 nmol/L(B), 50.00 nmol/L(C)], or 1 micromol/L of RO, or a combination of the two were added to the cells treated with 0.50 mmol/L of palmitic acid. Cell apoptosis was measured by flow cytometer. Phosphorylation-c-Jun N-terminal kinases (p-JNK) was detected by immuocytochemistry and Western blot. RESULTS: (1) The cells treated with palmitic acid has significantly higher apoptosis rates than controls (P < 0.05). (2) FGF-21 reduced apoptosis rates induced by palmitic acid (P < 0.05). But the apoptosis rates remained higher than controls (P < 0.05). A combination of FGF-21 and RO further reduced the apoptosis rates compared with FGF-21 alone (P < 0.05). (3) The cells treated with palmitic acid had higher expression of p-JNK than controls (P < 0.05). FGF-21 and a combination of FGF-21 and RO reduced the expression of p-JNK in cells treated with palmitic acid (P < 0.05). CONCLUSION: (1) Palmitic acid induces apoptosis in HIT-T15 cells in a dose dependent way. (2) The expression of p-JNK induced by palimitic acid is reduced by FGF-21 and the combination of FGF-21 and RO.

[Diagnostic value of salivary cortisol in Cushing's syndrome].

OBJECTIVE: To evaluate the usefulness of the measurement of midnight salivary cortisol (SC) in the initial diagnosis of Cushing's syndrome (CS). METHODS: A total of 18 patients with pathologically confirmed CS were recruited in the study. Thirteen patients with pure obesity and 36 healthy people served as controls. Salivary samples at 8:00, 16:00, 24:00 and 8:00 the next day after the 1 mg dexamethasone suppression test(DST) were collected by a commercially-available saliva collection device, and assayed by Electro Chemiluminescence Immuno Assay (ECLIA). RESULTS: There were highly significant correlations between salivary cortisol and plasma cortisol (PTC) at the 4 time points. The correlation coefficient was 0.73 (0.71, 0.74, 0.78 and 0.61 at the four time points, respectively) (P < 0.05). Midnight salivary cortisol level in Cushing's Syndrome [(10.58 +/- 5.17) nmol/L] was significantly higher than healthy people [(1.55 +/- 0.60) nmol/L]. The receiver operating characteristics curve (ROC) analysis showed a sensitivity of 100.00% and specificity of 84.00% at 8:00 with the cut-off point of 6.21 nmol/L. CONCLUSION: The measurement of midnight salivary cortisol is a convenience and noninvasive screening test for the initial diagnosis of Cushing's Syndrome.

[Relationship of 25(OH)VD with bone mass and other indicators in male patients with diabetes mellitus].

OBJECTIVE: To investigate the relationship of serum 25- Hydroxy D with bone mass density and other indicators in male patients with diabetes. METHODS: Bone mass density (BMD), serum 25- HydroxyD (25 (OH)VD) and several other biochemical indicators were measured in 82 male patients with diabetes, among whom 49 had osteoporosis. RESULTS: The diabetic patients with osteoporosis had higher tartrate-resistant acid phosphatase-5b (TRCAP-5b) and lower 25(OH)VD, testosterone (T), Dehydroepiandrosterone sulfate (DHEA-S), and bone-specific alkaline phosphatase (B-ALP) than those without osteoporosis (P < 0.05). The Parathormone (PTH) and albumin-creatinine ratio (UAlb/Cr) also increased in the diabetic patients with osteoporosis, but with no statistical significance. No difference was observed in glycosylated hemoglobin (HBA1c) between the diabetic patients with and without osteoporosis. The serum 25(OH)VD was negatively correlated with the duration of diabetes in both groups (P < 0.05), which was independent from the increase of age. The serum 25(OH)VD was positively correlated with T score of neck, ward, greater trochanter of femur and vertebrae lumbales, and T and DHEA-S in both patients with and without osteoporosis (P < 0.05). The 25(OH)VD was also positively correlated with PTH in the patients with osteoporosis. Negative correlation was noted between 25(OH)VD and B-ALP. There were no correlations between 25(OH)VD and TRCAP-5b, HBA1c and UAlb/Cr. CONCLUSION: Serum 25(OH)VD, T and DHEA-S may play an important role in the development of osteoporosis in male patients with diabetes mellitus.

[The response of serum ghrelin and PYY to oral glucose and steamed-bread tolerance test in nonobese and obese patients with type 2 diabetes].

OBJECTIVE: To investigate the response of serum ghrelin and PYY to oral glucose and steamed-bread load and their relationships to insulin and glucose in nonobese and obese patients with type 2 diabetes. METHODS: Ten obese subjects (Male: waist > or =90 cm, Female: waist > or =80 cm) and eleven nonobese subjects with type 2 diabetes were given oral glucose load and steamed-bread challenge in 2 consecutive days after blood glucose was controlled. The serum levels of ghrelin, PYY, insulin and glucose were measured with routine methods. RESULTS: (1) Either in oral glucose or steamed-bread load tests, both fasting serum PYY and ghrelin levels of obese subjects were significantly lower than those of nonobese subjects. After taking glucose or steamed-bread, all subjects were observed the increase of PYY and ghrelin levels, which reached the peak at 30 min and 60 min respectively. However, there were no significant difference found between nonobese and obese group at 30 min, 60 min and 120 min (P=NS). (2) In all subjects, fasting serum PYY, ghrelin concentrations were inversely associated with waist circumferences and BMI but not WHR. (3) No correlations were observed between serum PYY and insulin, glucose at any time points. The ghrelin and insulin levels showed a correlation at 0 min (r = -0.591, P = 0.005), however, no correlations were found at any other time points. When comparing PYY, ghrelin AUC with the AUC of insulin and glucose, no correlations were found. (4) Ghrelin level was positively correlated with QUICKI, however, no correlation between PYY concentrations and QUICKI was noted. CONCLUSIONS: In the subjects with type 2 diabetes, both PYY and ghrelin respond differently to glucose and bread, athough the calories are similar. PYY and ghrelin levels are inversely related to waist and BMI but not WHR. It is fasting ghrelin not PYY negatively associated with fasting insulin and positively with QUICKI.

[Impact of human isophane insulin on the evaluation of beta cell functions].

OBJECTIVE: To evaluate the beta cell functions with and without human Isophane insulin treatments. METHODS: Thirty patients with type 2 diabetes mellitus who followed the human Isophane insulin therapeutic regimen at bedtime were given 100 g steamed bread tests in two consecutive days. Then the human Isophane insulin treatments were stopped and the 100 g steamed bread tests were repeated in the next day. The fasting and 1, 2, 3 h after meal plasma glucose, serum insulin, C-peptide and proinsulin were measured. RESULTS: (1) The fasting and 1,2,3 h after meal plasma glucose increased while the serum insulin decreased after the human Isophane insulin treatments were stopped (P<0.05). (2) The fasting and 1, 2 h after meal C peptide increased (P<0.05) after the human Isophane insulin treatments were stopped. (3) The fasting and 1, 2, 3 h after meal proinsulin increased after the human isophane insulin treatments were stopped (P<0.05). (4) The area under the insulin curve decreased, while, the area under the C peptide increased after the human Isophane insulin treatments were stopped (P<0.05). CONCLUSION: Human Isophane insulin treatments should not be stopped to evaluate the beta cell functions of the patients who are undergoing Isophane insulin treatment.