Association between diabetic ketoacidosis and thyrotoxicosis

Three cases of diabetic ketoacidosis precipitated by thyrotoxicosis are presented. Two of them are young women with type 1 diabetes mellitus; the third case is a middle-aged woman with type 2 diabetes mellitus. All of them were diagnosed with Graves' disease. They typically showed tachycardia at rest in spite of correction of the metabolic disorder. Hyperthyroidism worsens glycemic control in diabetic patients and may precipitate diabetic ketoacidosis. On the other hand, women with diabetes have a higher prevalence of Graves' disease. Thus, in diabetic ketoacidosis without an obvious triggering factor, the presence of hyperthyroidism should be investigated, particularly in women. Received: 30 September 2001 / Accepted in revised form: 13 May 2002 Correspondence to A. Hernández-Mijares     

The impact of improved glycaemic control with GLP-1 receptor agonist therapy on diabetic retinopathy

Rapid improvement in glycaemic control with GLP-1 receptor agonist (RA) therapy has been reported to be associated with significant progression of diabetic retinopathy. This deterioration is transient, and continuing GLP-1 RA treatment is associated with reversal of this phenomenon. Pre-existent maculopathy, higher grade of retinopathy and longer duration of diabetes may be risk factors for persistent deterioration.     

Pantoprazole associated dyspepsia hypocalcemia and hyponatremia: A disproportionality analysis in FDA adverse event reporting system (FAERS) database

Background and study aimThe study was designed to detect novel Adverse Events (AEs) of pantoprazole by disproportionality analysis in the FDA (Food and Drug Administration) database of Adverse Event Reporting System (FAERS) using Data Mining Algorithms (DMAs). Pantoprazole, the most commonly over-utilized Over The Counter (OTC) medication, was selected to assess any short-term or long-term AEs. The study aimed to analyze the novel adverse events of pantoprazole using the FAERS database.Materials and methodsA retrospective case/non-case disproportionality analysis was performed in the FAERS database. This study was based on AEs reported to FAERS from 2006Q1-2021Q3. Openvigil 2.1 was used for data extraction. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) were applied to measure the disproportionality in reporting. A value of ROR-1.96SE > 1, PRR ≥ 2, and IC-2SD > 0 were considered as the threshold for a positive signal.ResultsA total of 1050 reports of dyspepsia, 7248 reports of hypocalcemia and 995 reports of hyponatremia were identified. A potential positive signal for dyspepsia (ROR-1.96SE = 2.231, PRR = 2.359, IC-2SD = 1.13), hypocalcemia (4.961, 5.45, 2.23) and hyponatremia (3.948, 4.179, 1.92) were identified for pantoprazole.ConclusionData mining in the FAERS database produced three potential signals associated with pantoprazole. As a result, further clinical surveillance is needed to quantify and validate potential hazards associated with pantoprazole-related adverse events.     

GLP-1 agonist treatment: implications for diabetic retinopathy screening

Rapid improvement in glycaemic control induced by GLP-1 agonist therapy could be yet another illustration of transient or permanent progression of diabetic retinopathy, similar to documented examples such as pregnancy and continuous subcutaneous insulin infusion. Specific guidelines would be needed to monitor this paradoxical phenomenon during treatment with GLP-1 agonists.     

Pantoprazole associated dyspepsia hypocalcemia and hyponatremia: A disproportionality analysis in FDA adverse event reporting system (FAERS) database

Background and study aimThe study was designed to detect novel Adverse Events (AEs) of pantoprazole by disproportionality analysis in the FDA (Food and Drug Administration) database of Adverse Event Reporting System (FAERS) using Data Mining Algorithms (DMAs). Pantoprazole, the most commonly over-utilized Over The Counter (OTC) medication, was selected to assess any short-term or long-term AEs. The study aimed to analyze the novel adverse events of pantoprazole using the FAERS database.Materials and methodsA retrospective case/non-case disproportionality analysis was performed in the FAERS database. This study was based on AEs reported to FAERS from 2006Q1-2021Q3. Openvigil 2.1 was used for data extraction. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) were applied to measure the disproportionality in reporting. A value of ROR-1.96SE > 1, PRR ≥ 2, and IC-2SD > 0 were considered as the threshold for a positive signal.ResultsA total of 1050 reports of dyspepsia, 7248 reports of hypocalcemia and 995 reports of hyponatremia were identified. A potential positive signal for dyspepsia (ROR-1.96SE = 2.231, PRR = 2.359, IC-2SD = 1.13), hypocalcemia (4.961, 5.45, 2.23) and hyponatremia (3.948, 4.179, 1.92) were identified for pantoprazole.ConclusionData mining in the FAERS database produced three potential signals associated with pantoprazole. As a result, further clinical surveillance is needed to quantify and validate potential hazards associated with pantoprazole-related adverse events.     

Addition of glucagon-like peptide-1 receptor agonist therapy to insulin in C-peptide-positive patients with type 1 diabetes

We aimed to test the hypothesis that addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to insulin in C-peptide-positive patients with type 1 diabetes (T1D) will result in a reduction in glycated haemoglobin (HbA1c) with reduced insulin requirements and a rise in C-peptide concentrations. We conducted a retrospective analysis of 11 normal-weight patients with T1D consecutively treated with a GLP-1RA in addition to insulin. Paired t tests were used to compare the changes in HbA1c, insulin doses, body weight, body mass index, and C-peptide concentrations prior to and 12 ± 1 weeks after GLP-1RA therapy. At the end of 12 ± 1 weeks of GLP-1RA therapy, HbA1c fell from 10.74 ± 0.96% (95 ± 10.5 mmol/mol) to 7.4 ± 0.58% (58 ± 6.3mmol/mol) (P < 0.01), body weight fell from 71 ± 2.0 to 69 ± 2 kg (P = 0.06), and total insulin dose was reduced by 64% from 33 ± 6 to 11 ± 5 units (P < 0.01). Five out of 10 patients did not require any insulin. C-peptide concentrations increased significantly from 0.43 ± 0.09 ng/ml (0.14 ± 0.02 nmol/L) to 1.42 ± 0.42ng/ml (0.47 ± 0.13 nmol/L) (P = 0.01). Addition of GLP-1RA therapy to insulin in normal-weight patients with T1D led to a reduction in HbA1c with reduced insulin requirements, a 3.5-fold increase in C-peptide concentrations and freedom from insulin therapy in 50% of patients who tolerated the GLP-1RA therapy over a period of 12 ± 1 weeks.     

A comparison of arterial and non-arterialized capillary blood gases in diabetic ketoacidosis

The results of acid-base and blood gas estimations in arterial and non-arterialized capillary blood have been compared in samples obtained simultaneously from patients presenting with diabetic ketoacidosis. Highly significant correlations were obtained for pH, pCO2 and bicarbonate measurements. Small but significant differences were observed with capillary pH slightly lower and capillary pCO2 and bicarbonate slightly higher than arterial values. These differences were of no clinical significance. Non-arterialized capillary samples are a reliable indicator of acid-base status in this form of metabolic acidosis and are preferable to repeated arterial puncture.     

The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists

The effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP-1RAs in non-clinical and clinical studies. GE was assessed following acute and chronic treatment with tirzepatide in diet-induced obese mice versus semaglutide or long-acting GIP analogue alone. Participants [with and without type 2 diabetes (T2DM)] from a phase 1, 4-week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. In mice, tirzepatide delayed GE to a similar degree to that achieved with semaglutide; however, these acute inhibitory effects were abolished after 2 weeks of treatment. GIP analogue alone had no effect on GE or on GLP-1's effect on GE. In participants with and without T2DM, once-weekly tirzepatide (≥5 and ≥4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy participants. In participants with T2DM treated with an escalation schedule of tirzepatide 5/5/10/10 or 5/5/10/15 mg, a residual GE delay was still observed after multiple doses. These data suggest that tirzepatide's activity on GE is comparable to that of selective GLP-1RAs.     

Profile of diabetic ketoacidosis at the National Diabetes and Endocrine Center in Tripoli,Libya, 2015

BackgroundDiabetic ketoacidosis (DKA) is a major acute metabolic complication of type I diabetes mellitus but may occur in type II diabetes during severe stressful conditions.AimThe aim of this study was to describe the clinical profile of DKA patients admitted to the National Diabetes and Endocrine Center in Tripoli, Libya, during 2015.Patients and methodsThe profiles of 490 patients admitted with DKA were retrospectively studied. All the data was collected from the patient files.ResultsMost of the patients (91.6%) were admitted to the intensive care unit. The mean age was 35.9 years. DKA was more common among young males with type I diabetes. The average duration of diabetes disease of the patient when admitted with DKA was 16.8 ± 8.2 years. The frequencies of patients admitted with mild, moderate or severe diabetic ketoacidosis were 49.8%, 32.7% and 17.8%, respectively. The most frequent causes of admission were insulin omission (21.8%), infection (20.2%), and wrong dose (11%). The cause of DKA was not known for 29.8% of the patients. DKA was more common among young males, and the rate increased with longer duration of the condition. Most of the patients (93.1%) were discharged in good health, and mortality was 0.6%.ConclusionMales and patients with a long duration of diabetes disease are more prone to develop DKA. The common causes of DKA were unknown in our study; however, admission of individuals with less serious illness, insulin omission, and infection may contribute to the development of DKA.     

糖尿病酮症酸中毒及(或)高渗状态横纹肌溶解症6例回顾分析

目的 了解糖尿病急症酮症酸中毒及(或)高渗状态横纹肌溶解症发生情况.方法 回顾分析52例糖尿病急症病例. 结果 横纹肌溶解症6例 (11.54%).横纹肌溶解症与非横纹肌溶解症血清肌酸磷酸激酶、肌红蛋白、葡萄糖、钠、有效血浆渗透压、钾水平分别是(3886±2817)μ/L vs (99±85)μ/L,( 4131±625)μg/L vs (84±58)μg/L, (59±24)mmol/L vs (28±14)mmol/L, (154±7)mmol/L vs (140±8)mmol/L, (375±31)mmol/L vs (310±21)mmol/L, (3.8±0.5)mmol/L vs (4.4±0.6)mmol/L; 肾功能衰竭100% vs 30.8%; 差异均有统计学意义 (P＜0.01). 结论 糖尿病酮症酸中毒及(或)高渗状态可能诱发横纹肌溶解症,宜重视肌酶检查.     

Changes in serum amylase, lipase and leukocyte elastase during diabetic ketoacidosis and poorly controlled diabetes

Diabetic ketoacidosis (DKA) is frequently associated with pancreatic enzyme abnormalities. In order to determine the main factors that lead to this increase, serum total amylase (TA), pancreatic amylase (PA), lipase (L) and leukocyte elastase (LE), an early predictor of acute pancreatitis, were measured in four groups of patients on admission. Group 1 consisted of 52 patients with DKA (age: 41.9 ± 19.2 years; blood glucose (Glc): 27.4 ± 11.5 mmol/L; pH: 7.20 ± 0.16; plasma bicarbonate: 10.5 ± 6.2 mmol/L; blood urea nitrogen (BUN): 0.60 ± 0.44 g/L; HbA_1C: 12.5% ± 2.8%). Group 2 consisted of 90 patients with poorly controlled non-ketotic diabetes (age: 53.4 ± 16.0; Glc: 14.3 ± 0.6; HCO₃ ⁻: 26.6 ± 3.2; BUN: 0.38 ± 0.20; HbA_1C: 11.3 ± 2.1). Group 3 consisted of 22 patients with well-controlled diabetes (age: 53.7 ± 12.8; Glc: 10.1 ± 5.2; HCO₃ ⁻: 27.4 ± 3.8; BUN: 0.36 ± 0.19; HbA_1C: 6.8 ± 0.8). Group 4 (controls) comprised 27 non-diabetic patients (age: 46.0 ± 15.0; Glc: 4.9 ± 0.5; HCO₃ ⁻: 28.4 ± 2.5; BUN: 0.30 ± 0.16; HbA_1C: 5.2 ± 0.7) (means ± SD). Increased enzyme activities were more frequent in group 1 (TA: 30.7; PA: 27.0; L: 36.5; LE: 73%) than in groups 2 (TA: 8.9; PA: 7.1; L: 8.9; LE: 45.5%), 3 (TA: 13.6; PA: 9.0; L: 18.1; LE: 31.8%) and 4 (TA: 7.0; PA: 3.0; L: 0.0; LE: 29.6%). Mean serum enzyme activities were significantly different in the 4 groups (ANOVA, P < 0.01) and were higher in group 1 than in groups 2, 3 and 4 (Student's t-test; group 1 vs 2 or 3 or 4: P < 0.001). In groups 1 + 2 + 3 + 4 (all patients), the four enzymes correlated with one another and also with Glc, BUN and HCO₃ ⁻ (P < 0.001). In group 1, TA correlated negatively with HCO₃ ⁻ (P < 0.001) and pH (P < 0.05); PA and L correlated positively with Glc and BUN (P < 0.01) and negatively with HCO₃ ⁻ (respectively, p < 0.01 and 0.05). PA correlated positively with pH (P < 0.01); LE correlated with Glc (P < 0.05) and BUN (P < 0.01). In conclusion, this study suggests that the serum levels of pancreatic enzymes increase with the degree of diabetic disequilibrium, and mainly correlate with metabolic factors such as hyperglycaemia, dehydration and acidosis. Increased pancreatic enzyme activities in patients with DKA, even in combination with abdominal pain, should not be diagnosed as acute pancreatitis; this could be important, particularly for younger clinicians. Received: 18 September 1998 / Accepted in revised form: 24 February 1999     

儿童及青少年糖尿病酮症酸中毒合并急性胰腺炎患者临床特点分析

目的了解儿童糖尿病酮症酸中毒(DKA)合并胰酶升高患者的临床特点、治疗经验及转归,为避免过度诊断急性胰腺炎(AP)和过度的长期禁食治疗提供证据。方法回顾性调查首都医科大学附属北京儿童医院内分泌遗传代谢中心2015年1月至2019年1月收治的年龄小于18岁的DKA合并胰酶升高的患儿,分析其临床症状、血淀粉酶、脂肪酶、血脂、胰腺影像学资料、治疗及临床转归等,总结治疗经验。数据采用中位数(上下四分位数)表示。结果4年共收治330例DKA患儿,38例(11.5%)合并胰酶升高,升高3倍以上的有22例(6.7%)。16例(4.8%)无胰腺影像学改变为疑诊AP,其中14例无腹痛症状,未经AP相关治疗,预后良好;1例有腹痛症状,常规进行DKA治疗,第2天腹痛症状缓解;另外1例合并腹痛症状的患者按照AP治疗12 d,在第14天开始尝试经口喂养,虽有胰酶复升高,但继续按原计划进行营养治疗病情无反复。6例(1.8%)合并胰酶升高患儿有影像学改变为确诊AP,4例有腹痛,6例均按照AP常规治疗,腹痛症状2~19 d缓解,胰酶2~15 d降至3倍以下,禁食时间3~60 d,随访5~32个月均无AP复发。结论DKA患儿胰酶增高并不少见,但AP发生率低,且预后好,是一个相对良性的过程,尚需更多数据证明。     

胰岛素泵和多次胰岛素皮下注射治疗对糖尿病酮症酸中毒和高渗昏迷的疗效比较

目的比较不同胰岛素给药方法对糖尿病酮症酸中毒（DKA）和糖尿病高渗性昏迷（DHC）的疗效。方法对DKA和DHC患者首先用静脉泵小剂量胰岛素持续输注,在生命体征平稳并能进半流食后分别用不同的胰岛素给药方式进行治疗：（1）持续皮下胰岛素输注（CSII）组;（2）常规4次皮下注射胰岛素（MSII）组。治疗目标为FBG≤7.0mmol/L、2hBG≤10mmol/L。结果两组每日胰岛素用量无统计学差异（P〉0.05）,但平均达标天数CSII组较MSII组明显缩短（P〈0.01）,CSII组血糖波动小,发生低血糖次数明显减少,且FBG及晚餐后2hBG控制亦明显优于MSII组（P〈0.01）。结论在治疗DKA和DHC时采用静脉泵连续小剂量胰岛素输注急救后,使用CSII较MSII能更快、更平稳、更有效地控制高血糖。     

GLP-1类似物在糖尿病肾病患者中的疗效分析

目的 观察胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)类似物对2型糖尿病早期肾病患者的肾脏保护作用.方法 2017年11月—2019年12月间选取使用GLP-1类似物并参与随访的2型糖尿病早期肾病患者30例,收集患者治疗6个月前后的体重,体质指数(body mass index,BM...     

六例糖尿病酮症酸中毒合并高脂血症和急性胰腺炎临床分析

目的提高临床医师对糖尿病酮症酸中毒(DKA)合并高脂血症(HL)和急性胰腺炎(AP)的认识。方法回顾性分析6例DKA合并HL和AP患者的临床资料。结果除DKA的临床特征外,还有:(1)6例患者均为中青年,年龄(34.2±4.1)岁,以急性腹痛就诊,均有腹部压痛;(2)入院时均有HL,次晨查甘油三酯(14．2-62．2 mmol/L),总胆固醇(8．9～29．4 mmol/L),治疗48-72h后甘油三酯降至(1.98 -5．39 mmol/L),总胆固醇降至(4．52-7．36 mmol/L);(3)AP发作期间5例患者血和(或)尿淀粉酶升高3倍以上,仅1例患者升高不到1倍;5例患者胰腺CT检查有AP改变,但其中3例患者B超显示胰腺正常;(4)治愈的5例患者以及时有效地纠正DKA和禁食治疗为基本措施,治疗后腹痛消失,血尿淀粉酶恢复正常。结论(1)以腹痛就诊的DKA患者,应查甘油三酯、血尿淀粉酶和腹部CT以排除AP;(2)纠正DKA和禁食是治疗暂时性显著HL和AP的关键。     

Bioactive GLP-1 in gut, receptor expression in pancreas, and insulin response to GLP-1 in diabetes-prone rats

Glucagon-like peptide-1 (GLP-1) is the most insulinogenic of the glucagon-like peptides secreted mainly by L cells in the small and large intestine in response to the ingestion of nutrients. It binds to a specific GLP-1 receptor (GLP-1R) on β-cells and can increase islet neogenesis and β-cell mass. It is not clear whether the transmission of information from the gut to islet β-cells by messengers such as GLP-1 is different in individuals who develop autoimmune diabetes. In the present study the expression of bioactive GLP-1 protein in the gut and its receptor in the pancreas was examined in diabetes-prone BioBreeding (BBdp) rats in the period before overt diabetes and in age-matched control, non-diabetes-prone BB (BBc) rats. An N-terminal directed antibody specific for the bioactive forms of GLP-1 (GLP-1^7-37 and GLP-1^7-36amide) was used to measure GLP-1 by radioimmunoassay in proximal, median, and distal gut. Pancreas GLP-1R area fraction, GLP-1R gene expression, and insulin content were analyzed, as were plasma GLP-1, glucose, and insulin. The concentration of GLP-1 protein in the jejunum and ileum of BBdp rats was lower than in BBc rats. Although these animals maintained normal blood glucose, there was impaired pancreatic endocrine function, characterized by low baseline insulin concentration in plasma and pancreas. GLP-1R mRNA expression was threefold less in islets isolated from BBdp rats, and GLP-1R⁺ islet area fraction in pancreas sections was decreased. When injected iv with GLP-1, BBdp rats displayed lower second-phase insulin response (and insulin/glucose ratios) compared with BBc rats. Thus, young BBdp rats displayed decreased concentrations of bioactive GLP-1 in jejunum and ileum, reduced GLP-1R in islets, and lower second-phase insulin response to iv GLP-1 than controls. The decrease in insulinogenic and islet β-cell mass-promoting signal from GLP-1 in BBdp rats may contribute to impaired glucoregulation and ineffective maintenance of normal islet mass that shifts islet homeostasis in favor of development of diabetes.