Plasma apolipoprotein A-IV levels decrease in patients with chronic pancreatitis and malabsorption syndrome

An immunochemical method was developed for measurements of serum levels of apolipoprotein A-IV (apo A-IV). Using this technique, we found decreased levels of apo A-IV in patients with chronic pancreatitis and malabsorption syndrome and these low levels of apo A-IV in a patient with malabsorption syndrome were overcome after appropriate oral nutrition. Thus, measurements of apo A-IV may provide a good index for the assessment of fat intake and absorption.     

长期高血糖对继发磺脲类药物失效患者胰岛β细胞功能的影响

目的　探讨长期高血糖对继发磺酰脲类药物 (SU )失效的 2型糖尿病 (T2DM )患者胰岛β细胞功能的影响。 　方法　继发SU失效的T2DM患者 51例 ,血糖控制前后均行标准馒头餐和精氨酸兴奋试验 ,血糖控制后另行格列苯脲试验。观察葡萄糖刺激的胰岛素反应 (IRG)、校正的胰岛 β细胞分泌功能指数 (MBCI)、精氨酸刺激的急性胰岛素反应 (AIRARG)。　结果　血糖控制前后AIRARG、IRG、MBCI的差异无显著意义。血糖控制前 ,格列苯脲有效组AIRARG 较失效组高 (P <0 0 5) ,IRG、MBCI两组间的差异无显著意义 ;血糖控制后 ,格列苯脲有效组AIRARG、IRG、MBCI均较失效组显著升高 (均P <0 0 5)。格列苯脲有效组血糖控制后IRG、MBCI均较控制前升高 (均P <0 0 5) ,而AIRARG在血糖控制前后的差异无显著意义。格列苯脲失效组血糖控制前后AIRARG、IRG、MBCI的差异无显著意义。　结论　长期高血糖损害胰岛β细胞功能 ,部分患者血糖控制后可使 β细胞功能部分恢复     

Effect of pancreatin on diabetes mellitus in chronic pancreatitis

The effect of pancreatin on insulinopenic diabetes was studied in 10 patients with chronic pancreatitis and exocrine function impairment. All patients were treated for 4 days in a randomized crossover trial with either pancreatin (6 x 2 capsules, 6 x 300 mg/d) or placebo. Blood glucose levels were determined 7 times every day and night. On day 5, the patients were studied by a glucose sensor with adjustment of blood glucose to 120 mg/dl until 8.00 in the morning. A test meal was applied with 2 capsules pancreatin or placebo. Blood glucose and plasma levels of C-peptide, glucagon and pancreatic polypeptide (PP) were determined in regular intervals for 4 hours. Blood glucose levels were not significantly altered by pancreatin. As shown by M-value according to Schlichtkrull (21.6 +/- 2.9 versus 32.4 +/- 7.4), there was a tendency towards smaller oscillations of blood glucose with pancreatin treatment. C-peptide levels (basal 0.081 +/- 0.008 ng/ml; postprandial 0.119 +/- 0.013 ng/ml) were not significantly altered by the administration of pancreatin. Basal and postprandial glucagon and PP plasma levels were not influenced by pancreatin. From these results, we conclude that pancreatic enzyme supplementation does not significantly alter the requirement of insulin in patients with diabetes mellitus secondary to chronic pancreatitis. Possible disturbances of the enteroinsular axis are discussed in this paper.     

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate—eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118–125) vs. 114 (108–120) mmHg; P = 0.01] and diastolic [73 (66–80) vs. 67 (70–73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1–9.9) vs. 7.5 (7.2–8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61–3.20) vs. 0.49 (0.31–0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.     

Effect of glucagon-like peptide 1(7-36)amide in insulin-treated patients with diabetes mellitus secondary to chronic pancreatitis

Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.     

Glucose counterregulation in diabetes secondary to chronic pancreatitis

Glucose counterregulation and hormonal responses after insulin-induced hypoglycemia were investigated in six patients with diabetes mellitus secondary to chronic pancreatitis, in seven with insulin-dependent (type I) diabetes mellitus, and in seven healthy subjects. Glucose counterregulation was identical in type I patients and in the patients with chronic pancreatitis, whereas both groups had impaired glucose recovery compared with the healthy subjects. The patients with chronic pancreatitis had no glucagon response to hypoglycemia, whereas epinephrine increased significantly. In an additional experiment, glucose recovery did not occur after hypoglycemia during concomitant beta-adrenoceptor blockade in these patients. In conclusion, glucose counterregulation is preserved but slightly impaired in patients with diabetes secondary to chronic pancreatitis, and the combination of total glucagon deficiency and pharmacological blockade of the metabolic actions of circulating epinephrine abolishes glucose counterregulation after hypoglycemia.     

1型糖尿病的二级预防临床研究进展

1型糖尿病是一种器官特异性自身免疫性疾病,目前尚无根治方法,患者需要终身胰岛素替代治疗。将1型糖尿病防患于未然,是患者和医师的梦想。近年来,易感基因和胰岛自身抗体检测方面的进展为1型糖尿病前期的预测和预防提供了理论依据和技术可能。此外,1型糖尿病二级预防的免疫干预治疗也取得了一定的成效。现对1型糖尿病二级预防的最新研究...     

Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.     

Gender,clamped hyperglycemia and arterial stiffness in patients with uncomplicated type 1 diabetes mellitus

Background: Diabetes mellitus (DM) reduces female gender-mediated protection against the development of renal disease possibly through effects on hyperglycemia. Women with DM also exhibit increased arterial stiffness, which may promote renal disease progression. The mechanisms responsible for increased arterial stiffness in women and the possible role of acute changes in ambient glycemia remain unknown.

Methods: Blood pressure, augmentation index (AIx), pulse wave velocity (PWV) and circulating mediators of the renin angiotensin system and nitric oxide (cGMP) were measured in men (n?=?22) and women (n?=?19) with uncomplicated type 1 DM under clamped euglycemic and hyperglycemic conditions.

Results: At baseline, men exhibited higher levels of angiotensin II (p?=?0.030) and lower cGMP levels (p?=?0.004), higher systolic blood pressure (124?±?2 versus 109?±?2?mmHg, p?p?p?p?p?=?0.853). In response to clamped hyperglycemia, systolic blood pressure increased in women (109?±?2 to 112?±?2?mmHg, p?=?0.005) but not men. Serum aldosterone increased and cGMP declined in women but not in men. Clamped hyperglycemia did not influence arterial stiffness in either group and radial and carotid AIx remained higher in women.

Conclusions: Arterial stiffness is higher in women with type 1 DM. This effect is not dependent on the effects of clamped hyperglycemia or neurohormonal activation.     

血管紧张素Ⅱ、炎性反应和2型糖尿病

以往临床研究发现高血压病患者发生2型糖尿病的风险增加,阻断肾素-血管紧张素系统(RAS)对于预防2型糖尿病的发生具有一定的保护作用.近期研究还表明,RAS可能直接参与了糖尿病发生发展过程.炎性反应是肥胖、2型糖尿病等代谢性疾病的重要分子基础.血管紧张素介导的氧化应激、炎性反应水平以及游离脂肪酸的增加在局部和全身都对机体产生重要的影响.     

Peculiarities of diabetes mellitus course in chronic pancreatitis

In order to identify features of the course pancreatic diabetes and discussion of the principles of conservative therapy were examined 66 patients with CP in age of 30 to 65 years (55 men, 11 women). Among them in 22 cases disease was followed with formation of calcification of pancreas, 13 - pancreatic cysts, and 5 revealed pseudo tumor form of CP, 10 patients had clinical and laboratory evidence of diabetes. Concerning CP complicated course were performed 14 resection and 11 draining operations on the pancreas. Based on clinical, instrumental and laboratory data was made the diagnosis of CP. Exocrine pancreatic function was assessed on the results of the breath test, using 13C-trioktanaine, which is applied for exocrine pancreatic function in vivo test. The content of C-peptide was investigated by enzyme-linked immunosorbent assay (ELISA). The data indicate pancreatic exocrine function decrease in patients with CP with complications and without complications in compare with the norm of 44% (24,3 +/- 1,7, 26,6 +/- 1,3%, respectively) according to the breath test. Significant decrease of the cumulative output tags based on the test data of patients with CP and pancreatic calcification, diabetes mellitus, after resection surgery with CP complications, and there were significant differences in compare with a group of patients with CP without complications (p = 0.5). The level of C-peptide in these groups of patients decreased significantly in compare with a group of patients with CP without complications, and patients with CP and Diabetes was reduced to 0,11 +/- 0,02 ng/ml, at a rate range of 0.7-1.9 ng/ml, ie below the minimum values of norm. Obtained a direct correlation between the level of C-peptide and indicators breath test in patients after resection HP (r = 0,84, p = 0,03). Antibodies to insulin in the whole group of studied patients CPs were negative, which proves the specific type of Diabetes at HP. Antibodies to insulin can be detected only at diabetes type 1. In 7 patients with CP and CD detected calcification, 5 patients performed resection surgery, 3 patients had calcification and conducted the pancreas resection. Thus, we can conclude that in patients with CP and formation of pancreas calcification, pancreas resections may predict the development of diabetes.     

Diagnosis and treatment of diabetes mellitus in chronic pancreatitis

Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus.It is a clinically relevant condition with a prevalence of 5%-10%among all diabetic subjects in Western populations.In nearly 80%of all type 3c diabetes mellitus cases,chronic pancreatitis seems to be the underlying disease.The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far.In contrast to the management of type 1 or type2 diabetes mellitus,the endocrinopathy in type 3c is very complex.The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition.General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus(up to 90%of all cases)is rather good.However,in a patient first presenting with diabetes mellitus,chronic pancreatitis as a potential causative condition is seldom considered.Thus many patients are misdiagnosed.The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy.In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency,preventing or treating a lack of fat-soluble vitamins(especially vitamin D)and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.     

Prevalence and clinical features of diabetes mellitus secondary to chronic pancreatitis in Japan; a study by questionnaire

The prevalence and clinical features of diagnosed mellitus secondary to chronic pancreatitis (CP) were assessed from northern (Hokkaido) to southern (Okinawa) Japan by means of a questionnaire to elucidate whether WHO-classified malnutrition-related diabetes mellitus (MRDM) exists in Japan. Of a total 17,500 diabetic patients, only two (0.011%)-one fibrocalculous pancreatic diabetes (FCPD) and one protein-deficient pancreatic diabetes (PDPD) - exhibited MRDM characteristics. A total of 649 CP were collected and classified into 268 cases with chronic alcoholic pancreatitis (CAP), 150 cases with chronic calcified pancreatitis (CCP) and 231 cases with other CP. The prevalence of diabetes mellitus was found to be 50.7% in CAP, 72.7% in CCP and 22.8% in other CP. Among all diabetics, 56.6% was noninsulin-dependent (NIDDM) and 26.4% insulin-dependent (IDDM). IDDM was most frequent in CP. Satisfactory and less than satisfactory glycemic control was obtained in approximately three quarters of all subjects. Only one quarter showed poor glycemic control. Insulin treatment was frequent in CAP (52.2%) and CCP (61.7%), but less in other CP (27.5%). The prevalence of diabetic retinopathy was observed in 33.1% of all subjects, nephropathy 21.0% and neuropathy 36.3%, respectively. The prevalence of complications, including macroangiopathy tended to be higher in CAP and CCP (40.3 and 56.9%) than in other CP (31.4%).     

Effect of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV in cultured rat hepatocytes.

We studied the effects of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV (apo A-IV) by cultured rat hepatocytes, using specific radioimmunoassay for rat apo A-IV. We also compared the effect of these hormones on the production of apo A-IV with those of albumin and apo A-I, reported previously. In the absence of hormones, apo A-IV and albumin in culture medium increased almost linearly for periods up to 24 h. The rates of accumulation of apo A-IV and albumin in the medium were 15.4 ng/mg cell protein per h and 1.2 micrograms/mg cell protein per h, respectively. The concentration of intracellular apo A-IV remained constant during the incubation. Insulin stimulated the production of albumin, but inhibited the production of apo A-IV dose-dependently. Glucagon inhibited the production of both albumin, and apo A-IV dose-dependently. Dexamethasone showed no significant effects on albumin production, but stimulated apo A-IV production. Thus, apo A-IV production in hepatocytes is regulated by several hormones with different effects on albumin production. The regulatory effects of these hormones on apo A-IV production were almost identical with the effects observed in a course of apo A-I synthesis, suggesting that the production of the two apoproteins are regulated by similar mechanisms.     

Practical strategies to normalize hyperglycemia without undue hypoglycemia in type 2 diabetes mellitus

Hypoglycemia is a common problem in pharmacologically treated patients with type 2 diabetes mellitus and can be a major barrier to achieving optimal glycemic control. For practitioners to minimize and treat hypoglycemia, it is important to understand the physiology, risk factors, and medications associated with hypoglycemia. Through education, lifestyle modifications, medication adjustments, and possibly re-examining glycemic goals, practitioners can reduce the incidence of hypoglycemia while still decreasing the risk of microvascular complications associated with hyperglycemia.