Muscle infarction in a young woman with brittle type 1 diabetes

We present the first case of muscle infarction in a 30-year-old woman who had a 5-year history of type 1 diabetes mellitus that was not complicated by nephropathy, retinopathy or neuropathy. All common causes of muscle infarction were excluded, particularly microangiopathy and a hypercoagulable state. The differential diagnosis included infection (pyomyositis, necrotic fasciitis), focal inflammatory myositis, vascular events, trauma, tumor and diabetic amyotrophy, all of which were excluded. In spite of good glycaemic control, her diabetes remained brittle; alternating states of transient acute hypoglycaemia and hyperglycaemia may have been responsible for the infarction. Brittleness resumed after treatment with subcutaneous insulin infusion using a portable pump. No recurrence of muscle infarction was observed during a 18-month follow-up.     

Characteristic changes in coronary artery at the early hyperglycaemic stage in a rat type 2 diabetes model and the effects of pravastatin

Background and purpose:

Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium-derived nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and the effects of pravastatin were examined in left anterior descending coronary arteries (LAD) from Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycaemic stage [vs. non-diabetic Long-Evans Tokushima Otsuka (LETO) rats].

Experimental approach:

Isometric tension, membrane potential and superoxide production were measured, as were protein expression of NAD(P)H oxidase components and endothelial NO synthase (eNOS).

Key results:

Superoxide production and the protein expressions of both the nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] oxidase components and eNOS were increased in OLETF rats. These changes were normalized by pravastatin administration. Not only acetylcholine (ACh)-induced endothelial NO production but also functions of endothelium-derived NO [from (i) the absolute tension induced by epithio-thromboxane A₂ (STA₂) or high K⁺; (ii) enhancement of the STA₂-contraction by a nitric oxide synthase (NOS) inhibitor; and (iii) the ACh-induced endothelium-dependent relaxation of high K⁺-induced contraction] or EDHF [from (iv) ACh-induced endothelium-dependent smooth muscle cell hyperpolarization and relaxation in the presence of a NOS inhibitor] were similar between LETO and OLETF rats [whether or not the latter were pravastatin-treated or -untreated].

Conclusions and implications:

Under conditions of increased vascular superoxide production, endothelial function is retained in LAD in OLETF rats at the early hyperglycaemic stage, partly due to enhanced endothelial NOS protein expression. Inhibition of superoxide production may contribute to the beneficial vascular effects of pravastatin.     

餐后高血糖与心血管危险因素的相关性

目的探讨餐后高血糖与心血管危险因素如血脂、血压、肥胖之间的相关性。方法对柳州市713名干部测量身高、体质量、腰围(WC)、血压,计算体质量指数(BMI),同时检测空服血糖(FBG)、餐后2h血糖(2hPBG)、血总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)等指标,根据1999年WHO糖尿病诊断标准,将受检者分为三组:正常糖耐量(NGT)、糖耐量低减(IGT)、糖尿病(DM),并进行统计学分析。结果①由NGT→IGT→DM,年龄、BMI、WC、SBP、DBP、TG的水平逐渐升高,且IGT和DM组均较NGT组显著升高(P<0.01),HDL-C水平显著降低(P<0.01)。②随着餐后血糖水平的增高,超重/肥胖、中心肥胖、血脂异常及高血压的检出率逐渐增高(P<0.001)。③2hPBG与年龄、BMI、WC、SBP、DBP、TG呈显著正相关(P<0.001),与HDL-C呈显著负相关(P<0.001),经偏相关分析,在控制其它影响因素后,2hPBG仍与WC、年龄、TG、DBP呈显著正相关(P<0.001)。结论餐后高血糖与中心肥胖、高TG、高血压独立相关,常聚...     

Comparison of hypertension, dyslipidaemia and hyperglycaemia between buckwheat seed-consuming and non-consuming Mongolian-Chinese populations in Inner Mongolia, China

1. In the present study, a total of 3542 Mongolians in two adjacent counties of Inner Mongolia, China, were randomly sampled in a cross-sectional study to assess the association of hypertension, dyslipidaemia and hyperglycaemia with lifetime consumption of buckwheat seed as a staple food. A sample group of 961 participants was also examined for fasting serum concentrations of lipids and glucose. 2. Frequent alcohol consumption significantly contributed to the high prevalence rate of hypertension in the pastureland Mongolian population. 3. The age-adjusted prevalence rate of hypertension in Kulun participants who consumed buckwheat seed as a staple food was 18.22% (95% confidence interval (CI): 16.95%, 19.49%), whereas that in Kezhuohou participants, who consumed corn as a staple food, was 23.31% (95% CI: 21.92%, 24.70%). A statistically significant difference was found between the two groups (P < 0.01). 4. Age-adjusted prevalence rates in Kulun participants compared with Kezhuohou participants for hypercholesterolaemia, hypertriglyceridaemia and abnormalities in low-density lipoprotein-cholesterol were 4.02% (95% CI: 2.24%, 5.80%) versus 7.76% (95% CI: 5.39%, 10.13%; P < 0.01), 26.58% (95% CI: 22.59%, 30.57%) versus 31.04% (95% CI: 26.59%, 35.13%; P < 0.05) and 4.66% (95% CI: 2.75%, 6.57%) versus 8.81% (95% CI: 6.30%, 11.32%; P < 0.01), respectively. 5. The age-adjusted prevalence rate of hyperglycaemia in Kulun participants was 1.56% (95% CI: 0.78%, 2.34%), whereas that in Kezhuohou participants was 7.70% (95% CI: 6.01%, 9.39%). The difference was significant (P < 0.01). 6. These findings suggest that the consumption of buckwheat seed may be a preventative factor for hypertension, dyslipidaemia and hyperglycaemia in the pastureland Mongolian population.     

Pharmaceutical care of patients with gestational diabetes mellitus

Rationale, aims and objective To investigate whether the introduction of a programme of optimising drug treatment, intensive education and self‐monitoring of patients diagnosed with gestational diabetes mellitus (GDM) at an early stage (<20 gestational weeks), will improve management outcomes as determined by objective measures of patient knowledge about diabetes, glycaemia control, maternal/neonatal complications, and health‐related quality of life. Methods The study was a randomized, controlled, longitudinal, prospective clinical trial performed at Al‐Ain Hospital, Al‐Ain, United Arab Emirates. Over an 18‐month period, patients diagnosed with GDM were recruited and were randomly assigned to either an intervention or a control group, in a ratio of 3:2. Intervention patients received a structured pharmaceutical care service (including education and introduction of intensive self‐monitoring) while control patients received traditional services. Patients were followed up from time of recruitment until 6 months postnatally at scheduled outpatient clinics. A range of clinical and humanistic outcome measures, including maternal and neonatal complications, were used to assess the impact of the intervention. Results A total of 165 patients (99 intervention, 66 control) completed the study. The intervention patients exhibited a range of benefits from the provision of the programme when compared with control group patients. Statistically significant (P < 0.05) improvements were shown in the intervention group for knowledge of diabetes, health‐related quality of life (as determined by the SF36), control of plasma glucose and HbA_1c, maternal complications [e.g. decreased incidence of pre‐eclampsia (5.1% vs. 16.7%), eclampsia (1.0% vs. 7.6%), episodes of severe hyperglycaemia (3.0% vs. 19.7%) and need for Caesarean section (7.1% vs. 18.2%)], and neonatal complications [e.g. decreased incidence of neonatal hypoglycaemia (2.0% vs. 10.6%), respiratory distress at birth (4.0% vs. 15.2%), hyperbilirubinaemia (1.0% vs. 12.1%) and large for gestational age (9.0% vs. 22.7%)]. Conclusion The research provides clear evidence that provision of pharmaceutical care adds value to the management of GDM as exemplified by improved maternal and neonatal outcomes.     

Nodular glomerulosclerosis in patients without any manifestation of diabetes mellitus

AIM/METHODS: Diabetic nodular glomerulosclerosis is considered to be the specific renal lesion of diabetes mellitus (DM). However, some cases, in which nodular glomerulosclerosis was found without any manifestation of DM, have also occasionally been reported. We clinicopathologically examined seven cases without a prior history of DM. They consisted of six men and one woman with a mean age of 57 years, and included three cases with family history of DM and six cases with hypertension. RESULTS: Mean body mass index was 26.2 +/- 5.9 (means +/- SD) kg/m(2) and haemoglobin A1c 5.3 +/- 1.1% or haemoglobin A1 7.0 +/- 0.6%. Mean plasma glucose levels were 5.3 +/- 0.7 mmol/L at fasting and 10.1 +/- 1.9 mmol/L at 2 h of 75 g OGTT (normal: 1 patient; impaired glucose tolerance: 4 patients; DM: 2 patients). None of them showed diabetic retinopathy in fundoscopic ophthalmoscopy. Mean serum creatinine was 268 +/- 215 micromol/L, urinary protein 5.2 +/- 4.0 g/day, and three patients had mild haematuria. Renal biopsy revealed typical nodular glomerulosclerosis, a negative deposition based on an immunofluorescence study, and neither any significant electron dense deposits nor fibrils on electron microscopy. CONCLUSION: These patients at presentation had no overt clinical manifestations of glucose intolerance. Diabetic nodular glomerulosclerosis can occur in patients without overt DM, suggesting the role of factors additional to prolonged hyperglycaemia in the pathogenesis of this disorder.     

Advanced glycation endproducts: what is their relevance to diabetic complications?

Glycation is a major cause of spontaneous damage to proteins in physiological systems. This is exacerbated in diabetes as a consequence of the increase in glucose and other saccharides derivatives in plasma and at the sites of vascular complications. Protein damage by the formation of early glycation adducts is limited to lysine side chain and N-terminal amino groups whereas later stage adducts, advanced glycation endproducts (AGEs), modify these and also arginine and cysteine residues. Metabolic dysfunction in vascular cells leads to the increased formation of methylglyoxal which adds disproportionately to the glycation damage in hyperglycaemia. AGE-modified proteins undergo cellular proteolysis leading to the formation and urinary excretion of glycation free adducts. AGEs may potentiate the development of diabetic complications by activation of cell responses by AGE-modified proteins interacting with specific cell surface receptors, activation of cell responses by AGE free adducts, impairment of protein-protein and enzyme-substrate interactions by AGE residue formation, and increasing resistance to proteolysis of extracellular matrix proteins. The formation of AGEs is suppressed by intensive glycaemic control, and may in future be suppressed by thiamine and pyridoxamine supplementation, and several other pharmacological agents. Increasing expression of enzymes of the enzymatic defence against glycation provides a novel and potentially effective future therapeutic strategy to suppress protein glycation.     

Continuous glucose monitoring as a tool to identify hyperglycaemia in non‐diabetic patients with acute coronary syndromes

Aim To explore the occurrence and the distribution of glucose excursions > 7.8 mmol/l by continuous glucose monitoring (CGM) in non‐diabetic patients admitted with acute coronary syndrome (ACS). Methods Twenty‐one non‐diabetic patients without baseline hyperglycaemia admitted for ACS wore a continuous glucose monitoring system (CGMS) for a median period of 45.6 h. Occurrence and 24‐h distribution of time spent with blood glucose > 7.8 mmol/l (TS > 7.8) were retrospectively investigated. Results CGMS data disclosed time spent > 7.8 in 17 patients, whereas only seven of them showed at least one capillary blood glucose test value above the threshold for the same time period. Glucose excursions were detectable earlier from CGMS data. Hyperglycaemia was detected most frequently in the morning, more than 2 h after breakfast. Conclusions CGM discloses early and frequent hyperglycaemia in non‐diabetic patients with ACS. Intensive glucose monitoring during the morning time period is the most efficient in screening for hyperglycaemia and could be a valuable guide to initiating insulin therapy and to further investigate outcomes in ACS.     

The Hyperglycaemic Activity of Some Catecholamines and the Effect of α- and β-Adrenergic Blocking Compounds in the Mouse

In order to classify the receptors involved in the hyperglycaemic response to catecholamines in the mouse, the relative potency of noradrenaline, adrenaline and isoprenaline in the induction of hyperglycaemia has been tested by giving increasing doses from 10 μg/kg to 1 mg/kg of one of the amines intraperitoneally. Following catecholamine administration the maximal concentration of glucose in the blood occurred between 10 and 30 min. and amounted to about 300 mg%. The relative potency was: adrenaline > noradrenaline while isoprenaline was inactive. The antagonistic effect on adrenaline induced hyperglycaemia of the α-adrenergic blocking compounds: phenoxybenzamine HCl (dibenzyline®) and phentolamine (regitin®) and the β-adrenergic blocking compounds: 1-(isopropylamino)-3-(o-phenoxyphenoxy)-2-propanol (Ph QA 33) and propranolol were tested by giving 1 and 10 mg/kg intraperitoneally 30 min. before the administration of adrenaline. Only phentolamine at the highest dose level was capable of preventing the hyperglycaemic response to adrenaline. Phenoxybenzamine, Ph QA 33 and propranolol proved to be inactive. It is concluded that the mechanism of adrenaline induced hyperglycaemia in mice cannot be explained simply by an α- and/or β-receptor activation.     

Continuous monitoring of blood sugar in brittle diabetics

Summary The blood glucose was measured continuously for periods of up to twenty-nine hours in five patients. The method, which does not require heparinization of the patient, is described. — Three unstable diabetics were investigated. In two, diabetic control was considerably improved as a result of alterations made to their therapeutic regime following this investigation. The symptoms of the third diabetic patient were due to complications of diabetes rather than to the disease itself. — The results in these three patients are contrasted with those obtained in two acromegalics (one of whom was also diabetic). Attention is drawn to the occurrence of fasting hyperglycaemia in the early hours of the morning in the brittle diabetics and to the rapidity with which the blood glucose rises. It is thought that growth hormone is not directly responsible for this hyperglycaemia, since marked insulin sensitivity is maintained.

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Dauermessung der Blutzuckerspiegel bei labilen Diabetikern

Zusammenfassung Bei 5 Patienten wurden die Blutzuckerspiegel fortlaufend über Zeiträume von bis zu 29 Std. bestimmt. Die Methodik, die keine Heparinisierung des Patienten erforderlich macht, wird beschrieben. Drei nicht stabile Diabetiker wurden untersucht. Bei zwei Patienten besserte sich die Diabetes-Einstellung beträchtlich auf Grund von Änderungen in der Therapie, die auf Grund dieser Untersuchungsergebnisse vorgenommen wurden. Die Symptome des dritten Diabetikers waren in erster Linie auf Diabeteskomplikationen und nicht so sehr auf die Krankheit selbst zurückzuführen. Die Ergebnisse bei diesen drei Patienten werden mit denen von 2 Akromegalen verglichen, von denen einer ebenfalls einen Diabetes aufwies. Es wird besonders auf das Vorkommen einer Nüchtern-Hyperglykämie in den frühen Morgenstunden bei labilen Diabetikern und auf die Geschwindigkeit des Blutzuckeranstieges hingewiesen. Es wird angenommen, daß das Wachstumshormon nicht direkt für diesen Blutzuckeranstieg verantwortlich ist, da die Insulinempfindlichkeit erhalten bleibt.

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Contrôle continu de la glycémie chez des diabétiques instables

Résumé La glycémie a été mesurée continuellement pendant des périodes allant jusqu'à 29 h chez 5 malades. On décrit la méthode qui n'exige pas l'héparinisation du malade.— Trois diabétiques instables ont été étudiés. Chez deux d'entre eux l'équilibre diabétique a été considérablement amélioré par suite des modifications apportées à leur régime thérapeutique qui a suivi cette investigation. Les symptômes du troisième diabétique étaient dus à des complications du diabète plutôt qu'au diabète lui-même. — Les résultats chez ces trois patients sont comparés avec ceux obtenus chez deux acromégales (dont l'un était aussi diabétique). On attire l'attention sur l'apparition de l'hyperglycémie à jeun dans les premières heures de la matinée chez les diabétiques instables et sur la rapidité avec laquelle la glycémie s'élève. On pense que l'hormone de croissance n'est pas directement responsable de cette hyperglycémie, puisqu'une sensibilité marquée à l'insuline est maintenue.