Improved Beta Cell Function,with Reduction in Secretion of Intact and 32/33 Split Proinsulin,after Dietary Intervention in Subjects with Type 2 Diabetes Mellitus

Diet in Type 2 diabetes often reduces both hyperglycaemia and weight and both these factors may contribute to improvement in beta cell function. Sixty-nine subjects with newly diagnosed Type 2 diabetes had their glucose, insulin, intact and 32/33 split proinsulin measured at diagnosis, and after 16 (12–20) weeks of conventional diet. In the whole group following diet there was reduction in weight (p < 0.0001), Haemoglobin A₁ (p < 0.0001), and fasting glucose (p < 0.0001). There was a fall in fasting intact proinsulin (p < 0.03), 32/33 split proinsulin (p < 0.0001), and the percentage of fasting proinsulin to total insulin-like molecules (p < 0.0001). Subjects were separated according to weight loss (group 1 < 0.5 kg, group 2 0.5–4 kg, group 3 > 4 kg). Only subjects in group 3 (mean weight loss 6.2 kg) had a fall in fasting insulin (p < 0.04). The fasting glucose achieved following diet was positively correlated with the initial fasting glucose (r = 0.7) and negatively correlated with the degree of insulin deficiency at diagnosis (with the initial 30 min insulin r = ?0.62). The effect of diet on the final concentration of insulin, 32/33 split proinsulin and intact proinsulin was examined using multiple regression. The final insulin concentration was determined by the initial BMI and absolute weight loss, 32/33 split proinsulin concentration by the initial fasting glucose and absolute glucose fall, and intact proinsulin concentration by a combination of both weight loss and glucose reduction. We conclude that diet without weight loss increases the insulin secreted relative to the glucose concentration and reduces the concentration of proinsulin-like molecules. Weight loss reduces insulin resistance thereby lowering the insulin and intact proinsulin concentrations.     

The Relationship Between Plasminogen Activator Inhibitor-1 and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Mellitus

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAI-1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin-resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAI-1, 17.6 (11.1–28) vs 8.4 (4.9–14.1) IU ml^?1, p < 0.001. PAI-1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r=0.66, p < 0.001; insulin resistance, r = 0.54, p< 0.005 and urinary albumin excretion, r=0.48, p < 0.01, but not HbA_1c or fasting glucose. PAI-1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAI-1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.     

Effect of Sulphonylurea Therapy on Plasma Insulin,Intact and 32/33 Split Proinsulin in Subjects with Type 2 Diabetes Mellitus

This study was undertaken to clarify the effect of sulphonylurea therapy on beta cell function in 27 subjects with newly diagnosed Type 2 diabetes mellitus. Plasma glucose, insulin, intact and 32/33 split proinsulin were measured at diagnostic OGTT. After 8–12 weeks on a conventional diet, subjects with a fasting glucose > 9 mmol I^?1 (n = 12) were commenced on sulphonylurea therapy. At diagnosis, the sulphonylurea requiring group were more hyperglycaemic (p < 0.0001), less obese (p<0.05) and more insulin deficient with a lower 30 min insulin (p < 0.0002) than the diet group. Following dietary intervention in the sulphonylurea group, weight remained unchanged but there was a reduction in fasting glucose (p < 0.009). Fasting insulin, intact proinsulin, and 32/33 split proinsulin remained unchanged. After 12 weeks of sulphonylurea therapy there was a weight gain of 1.5 kg (p < 0.01), but a reduction in fasting glucose (p < 0.0001). Fasting insulin and intact proinsulin increased (p < 0.004) but 32/33 split proinsulin remained unchanged. There was a significant increase in both the fasting insulin to glucose ratio (p < 0.005), and the intact to 32/33 split proinsulin ratio (p < 0.02). Final fasting glucose following sulphonylurea therapy was positively correlated with the initial intact and 32/33 split proinsulin and the fasting glucose following dietary treatment. It is clear from this work that sulphonylureas have a complex effect on beta cell physiology and as well as stimulating release of insulin they increase the release of intact proinsulin but not that of 32/33 split proinsulin, hence they increase the intact to 32/33 split proinsulin ratio.     

Diet Treatment of Newly Presenting Type 2 Diabetes Improves Insulin Secretory Capacity,but Has No Effect on Insulin Sensitivity

Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity. Median fasting glucoses were 9.6 mmol l^?1 at diagnosis and 8.5 mmol l^?1 at 3 months (NS). Median fasting insulin was 9.3 mU l^?1 at diagnosis and 11.7 mU l^?1 at 3 months (NS). Median fasting C-peptide was 0.58 nmol l^?1 at diagnosis and 0.64 nmol l^?1 at 3 months (p < 0.05). Median achieved plasma insulin increased from 13.8 mU l^?1 at diagnosis to 17 mU l^?1 at 3 months (p < 0.02); median achieved plasma C-peptide increased from 0.72 nmol l^?1 at diagnosis to 0.81 nmol l^?1 at 3 months (p < 0.002). Modelled beta-cell function rose from median 26 % at diagnosis to 37 % at 3 months (p < 0.02). Modelled insulin sensitivity showed no significant change (median 0.31 at diagnosis, 0.27 at 3 months, NS). Elevation of achieved C-peptide was positively correlated with weight loss (R_s = 0.53, p < 0.05), but not with change in fasting glucose. Diet treatment of newly diagnosed Type 2 diabetes, with modest weight loss, results primarily in improvement of insulin secretory capacity, rather than insulin sensitivity.     

Immunoradiometric assay of insulin,intact proinsulin and 32–33 split proinsulin and radioimmunoassay of insulin in diet-treated Type 2 (non-insulin-dependent) diabetic subjects

Summary Plasma insulin, intact proinsulin and 32–33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 ± 1.0 mmol/l (mean ± SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay were 33 higher than insulin and 16 % higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32–33 split proinsulin. The ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0 % (6.8–21.0 %, 1 SD range) and 6.3 % (4.0–9.8 %), respectively,p < 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non-diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/1,p < 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/1,p < 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/1,p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination ( subnormal responses in six of ten and eight of ten, respectively). Thus, raised proinsulin and proinsulin:total insulin ratio are not necessarily a feature of mild diet-treated Type 2 diabetic patients with subnormal insulin responses to glucose.     

老年2型糖尿病血浆脂联素与瘦素和胰岛素的关系

目的 :探讨血浆脂联素、瘦素和胰岛素在老年 2型糖尿病和 2型糖尿病伴高血压患者的水平及其相互关系。方法 :对 75例居住在武汉的被检者同时采集病史、进行体格检查并留取血浆 ,测定其血糖、胰岛素、瘦素、血脂和脂联素的水平。结果 :①老年糖尿病组与糖尿病合并高血压组之间的血浆脂联素水平无显著性差异 ,但二者均低于对照组 ;老年与非老年对照组之间的血浆脂联素水平无显著性差异。②简单相关分析提示脂联素与体重指数、空腹和餐后 1h和 2h血糖、胰岛素抵抗指数、高血压、瘦素、载脂蛋白A负相关 ,与高密度脂蛋白正相关 ;采用逐步回归法分析 ,校正其它参数 ,体重指数、瘦素和空腹血糖为影响脂联素水平的独立因素。结论 :老年糖尿病患者的血浆脂联素水平降低 ,在肥胖、2型糖尿病、瘦素、胰岛素和脂联素之间可能存在互动的相关性     

积雪草对2型糖尿病大鼠胰岛素抵抗影响的研究

目的：观察积雪草提取液对2型糖尿病大鼠胰岛素抵抗（IR）的影响。方法：尾静脉注射链脲佐菌素（STZ）并高糖高脂饲料喂养诱导2型糖尿病大鼠模型。随机分为积雪草低剂量组、积雪草高剂量组、二甲双胍组、模型组与正常组。观察体重、口服糖耐量试验（OGTT）、血甘油三酯（TG）、总胆固醇（TC）、空腹血清胰岛素（FINS）、胰岛素抵抗指数（IRI）（IRI=FINS×FPG/22.5）的改变。结果：①模型组大鼠体重明显增加（P〈0.01）,OGTT、TG、TC水平较正常对照组明显增高（P〈0.01）;②药物治疗后,积雪草组及二甲双胍组体重、血糖、血脂、IRI均明显降低（P〈0.01）;③积雪草高剂量组在降低血糖、血脂水平方面与二甲双胍组之间无明显的统计学差异（P〉0.05）,在降低IRI方面与二甲双胍组之间有明显的统计学差异（P〈0.01）。结论：2型糖尿病大鼠存在糖脂代谢紊乱及IR,积雪草可明显降低其血糖水平、减轻体重、降低血脂及IRI,其降低血糖、血脂水平的作用与二甲双胍相当,其降低IRI水平的作用优于二甲双胍。     

Hyperinsulinaemia is Associated with Stimulation of Cholesterol Synthesis in Both Type 1 and Type 2 Diabetes

The effect of hyperinsulinaemia and hyperglycaemia on cholesterol synthesis was examined in lymphocytes from diabetic subjects. The first part of the study involved the provocation of hyperinsulinaemia by consumption of a carbohydrate-rich meal, in obese patients with Type 2 diabetes mellitus. Cholesterol synthesis was measured before and 4 h after completing the meal. Results were compared to groups of obese non-diabetic patients and to control subjects. Analysis of the three groups demonstrated that the percentage change in cholesterol synthesis was directly proportional to the percentage rise in serum insulin (r = 0.49, p < 0.05). This physiological study demonstrated that postprandial hyperinsulinaemia promoted cholesterol synthesis; however, we could not estimate the effect of the meal on cholesterologenesis. To study hyperinsulinaemia in isolation, we examined the effects of varying insulin infusion rates for 4 h at either low or high levels of serum glucose using the glucose clamp technique in young Type 1 diabetic patients. Cholesterol synthesis in lymphocytes was again measured before and after the study period. Hyperinsulinaemia stimulated cholesterol synthesis (+28.6%, p < 0.05) but hyperglycaemia alone did not exhibit this effect (-1.7% NS). The combination of hyperinsulinaemia and hyperglycaemia produced the greatest increase in cholesterol synthesis (+ 51.4%, p < 0.05) but this increase was not significantly different from hyperinsulinaemia alone. The percentage increase in serum insulin levels was again proportional to the percentage change in cholesterol synthesis (r = 0.46, p < 0.05).     

胰岛素泵治疗2型糖尿病合并妊娠患者的疗效分析

目的分析胰岛素泵治疗2型糖尿病合并妊娠患者的疗效。方法选择2018年2月—2019年1月在该院接受治疗的56例2型糖尿病合并妊娠患者,随机分为观察组和对照组,其中观察组患者选择胰岛素泵治疗,对照组患者采取传统的多次皮下注射方式进行治疗。经过治疗干预后比较两组患者的血糖情况、体质量指数、并发症情况及妊娠结局。结果经过治疗干预,观察组患者的空腹血糖含量为(5.17±0.68)mmol/L,并发症发生率为17.85%,体质量指数为(21.22±2.03)kg/m2,对照组患者的空腹血糖含量为(5.62±0.98)mmol/L,并发症发生率为32.14%,体质量指数为(24.78±2.04)kg/m2。且统计结果显示,观察组患者的妊娠结局要在一定程度上优于对照组。结论采取胰岛素泵治疗2型糖尿病合并妊娠可以取得较好的治疗效果,且有助于降低患者并发症的发生率,改善患者妊娠结局。     

Insulin Loss at the Injection Site in Children with Type 1 Diabetes Mellitus

A simple filter paper technique is described for demonstrating and measuring insulin loss at the injection site in children with type 1 diabetes mellitus. Using this technique in a cohort of 19 children during a 7-day period, measurable fluid was demonstrated at the injection site in 68% of children at least once and was present following 23% of all injections. In nearly 80% of cases the insulin loss probably represented less than 1 unit but could on occasions be 2 units or more or up to 18% of the injected dose. Insulin losses were observed following injections given by children themselves and by parents. There was no significant relationship between insulin dose and insulin loss. Insulin losses at the injection site are frequent and, although usually small in amount, are a potential source of blood glucose variability.     

UK Prospective Diabetes Study V. Characteristics of Newly presenting Type 2 Diabetic Patients: Estimated Insulin Sensitivity and Islet B-cell Function

In 713 newly diagnosed Caucasian diabetic patients aged 25–65 inclusive, insulin sensitivity and islet B-cell function were estimated from fasting plasma glucose and insulin concentrations by Homeostasis Model Assessment. Insulin sensitivity was reduced in obese subjects. It was also slightly lower in male than in female diabetic patients, in those who were sedentary and in those with high fasting plasma glucose concentrations. The estimated B-cell function was particularly impaired in patients with a high fasting plasma glucose and in those with normal rather than excess body weight. Whilst diabetes can present in normal weight patients with marked deficiency of B-cell function, presenting patients often have only a moderate impairment of B-cell function with markedly impaired insulin sensitivity secondary to obesity, physical inactivity, or being male.     

不同胰岛素注射方法治疗2型糖尿病并发感染临床疗效对比观察

目的研究不同胰岛素注射方法治疗2型糖尿病并发感染的临床疗效。方法该次纳入2018年7月—2019年6月期间该院收治的96例2型糖尿病并发感染患者展开研究,按照随机数字表法分为两组,对照组48例实施胰岛素三短一长法强化注射,观察组48例予以胰岛素泵持续皮下注射。将两组的临床疗效、治疗相关指标、并发症发生情况进行比对。结果观察组2型糖尿病并发感染患者的临床总有效率高于对照组(P<0.05);观察组患者治疗后的空腹血糖、餐后2 h血糖水平、血糖达标时间、胰岛素日用量、感染控制时间均优于对照组,并发症发生率低于对照组(P<0.05)。结论相较于胰岛素三短一长法强化注射法,胰岛素泵持续皮下注射治疗2型糖尿病并发感染患者更加安全有效,可促进血糖及感染控制效果的提升。     

胰岛素强化治疗在初发2型糖尿病患者中临床应用的效果分析

目的 探究胰岛素强化治疗在初发2型糖尿病患者中临床应用效果.方法 选择2018年5月—2019年12月该院收治的100例初发2型糖尿病患者,按入院的先后顺序分为实验组和对照组,每组50例.对照组采用口服降糖药治疗,实验组采用胰岛素强化治疗,对比两组患者的血糖指标,治疗效果以及空腹胰岛素(Fins),胰岛β细胞功能指数(...     

个体化糖尿病教育对初次使用胰岛素的2型糖尿病患者的疗效评价

目的探讨针对初次应用胰岛素治疗的2型糖尿病患者开展个体化糖尿病教育的临床价值。方法对照组患者开展常规的糖尿病健康教育,观察组则在该基础上开展个体化糖尿病教育。结果两组健康教育前SDSCA-6依从性量表各维度评分较低;健康教育后观察组SDSCA-6依从性量表各维度评分均高于对照组(P<0.05);两组健康教育FPG、2 hPG、HbAlc前较高(P>0.05);健康教育后观察组FPG、2 hPG、HbAlc低于对照组(P<0.05)。结论对于首次应用胰岛素治疗的2型糖尿病患者进行个体化的糖尿病教育可以有效提升其依从性,并更好的控制血糖水平。     

新诊2型糖尿病患者血清总胆红素与外周动脉内膜中膜厚度的关系

目的 初步探讨新诊2型糖尿病患者血清总胆红素与外周动脉内膜中膜厚度的关系.方法 357例新诊2型糖尿病患者,根据是否有外周动脉内膜中膜增厚分为内膜中膜增厚组(178例)和内膜中膜正常组(179例),比较两组血清总胆红素浓度;根据患者血清总胆红素浓度由低到高将患者分为四组:低胆红素组、较低胆红素组、较高胆红素组、高胆红素组,比较四组患者外周动脉内膜中膜厚度;采用Logistic回归分析法分析新诊2型糖尿病患者外周动脉内膜中膜厚度增厚的危险因素.结果 内膜中膜增厚组血清总胆红素浓度比内膜中膜正常组降低,两组比较差异有显著性(P<0.05).根据血清总胆红素浓度进行分组的四组患者,外周动脉内膜中膜厚度低胆红素组高于高胆红素组,差异有显著性(P<0.01).Logistic回归分析显示,血清总胆红素、年龄和收缩压进入回归方程.结论 低血清总胆红素可能是新诊2型糖尿病外周动脉内膜中膜增厚的独立危险因素.     

胰岛素+达格列净治疗2型糖尿病的效果和对患者血糖的影响探讨

目的 探讨胰岛素+达格列净治疗2型糖尿病的效果和对患者血糖的影响.方法 将该院2018年10月—2020年6月期间治疗2型糖尿病患者88例作为研究对象,所有患者均采用常规降糖药物胰岛素进行治疗,根据是否联合应用达格列净药物分为两组,每组44例,对照组给予常规降糖药物进行治疗,试验组则在对照组基础上联合应用达格列净片,所...     

The Relationship Between Obesity,Plasma Immunoreactive Insulin Concentration and Blood Pressure in Newly Diagnosed Indian Type 2 Diabetic Patients

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24–59) years, IGT 48 (29–64) years, diabetic 43 (29–60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m^?2 (17.2–29.9), IGT 26.0 kg m^?2 (19.8–33.9), diabetic 24.2 kg m^?2 (19.3–32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70–0.98), IGT 0.88 (0.75–0.98), diabetic 0.89 (0.75–1.00)). Blood pressure was significantly higher in both IGT (systolic 127mmHg (108–162), diastolic 80 mmHg (66–99)) and diabetic patients (systolic 130 mmHg (104–160), diastolic 84 mmHg (66–102)) compared to non-diabetic controls (systolic 120 mmHg (100–151), diastolic 80 mmHg (60–94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r= 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r= ? 0.25, p<0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r= 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r= 0.30, p < 0.001, post glucose r = ? 0.20, p < 0.05) but not to C-peptide concentrations. Multivariate analysis revealed that systolic blood pressure in diabetic patients was related to BMI (p < 0.01) and fasting immunoreactive insulin (p < 0.05) while diastolic blood pressure was related to BMI (p < 0.001) and waist-hip ratio (p < 0.01). Thus, blood pressure is associated with obesity even in our relatively non-obese population and it is also associated with plasma immunoreactive insulin concentrations. The mechanism of these associations remains to be established.     

Frequency and Symptoms of Hypoglycaemia Experienced by Patients with Type 2 Diabetes Treated with Insulin

This study ascertained the prevalence of severe hypoglycaemia and loss of awareness of hypoglycaemia in patients with Type 2 diabetes treated with insulin. One hundred and four sequentially selected Type 2 diabetic patients were compared with 104 patients with Type 1 diabetes who were matched for duration of insulin therapy. The patients were interviewed using a standardized questionnaire. During treatment with insulin, 18 Type 2 patients had experienced fewer than two episodes of hypoglycaemia, while 86 had experienced two or more episodes; 80 (93%) reported normal awareness, six (7%) reported partial awareness, and none had absent awareness of hypoglycaemia. All 86 Type 1 diabetic patients matched to the 86 Type 2 patients had experienced multiple episodes of hypoglycaemia; 71 (83%) had normal awareness, 14 (16%) had partial awareness and one patient (1%) reported absent awareness of hypoglycaemia. The Type 1 patients who had altered awareness of hypoglycaemia had longer duration of diabetes and insulin therapy (normal awareness: 5 (1–17) years (median (range)) vs partial awareness: 9 (3–18) years, p < 0.01). Similarly, Type 2 patients with altered awareness had longer duration of diabetes (normal awareness: 11 (2–25) years vs partial awareness: 19 (8–24) years, p < 0.02) and had received insulin for longer (normal awareness: 3 (1–18) years vs partial awareness: 12 (6–17) years, p < 0.001). Severe hypoglycaemia in the preceding year had occurred with a similar prevalence in the Type 2 patients (9 (10%)) and Type 1 patients (14 (16%)), but was more frequent in those patients with partial awareness both in Type 1 patients (normal awareness: 3 (4%) vs partial awareness: 11 (73%), p < 0.001) and in Type 2 patients (normal awareness: 3 (4%) vs partial awareness: 6 (100%), p < 0.001). Although the symptoms of hypoglycaemia were idiosyncratic in individual Type 2 patients, the range and prevalence of specific symptoms were similar to those described by the patients with Type 1 diabetes.