Clinical characteristics and outcomes of diabetic ketoacidosis in Pakistani adults with Type 2 diabetes mellitus.

AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Pakistani adult population with Type 2 diabetes mellitus. METHODS: We reviewed the medical records of all adult patients admitted with a diagnosis of DKA and Type 2 diabetes mellitus (DM) and followed their clinical course and outcome. Follow-up data were obtained by chart review or telephone contact where necessary. RESULTS: Fifty-seven patients fulfilled criteria for inclusion in the study. Their mean age was 48 +/- 7 years. The mean body mass index was 25.5 +/- 6.2 kg/m2. Forty-nine had a prior history of Type 2 DM but DKA was the initial presentation in 14%. Nine were on no treatment, 40 were using oral hypoglycaemic agents and eight were on insulin. A history of prior DKA was noted in eight patients. Infections were the most common precipitating factor (63%). There were 12 deaths. Follow-up after a period ranging between 12 and 43 months revealed that 30/45 patients remained on OHA without recurrence of DKA. CONCLUSION: This report highlights the need for the growing recognition of DKA occurring in adults with Type 2 DM in the South Asian population. Mortality rates are unacceptably high but the majority of survivors remain insulin independent.     

Pathophysiology of ketoacidosis in Type 2 diabetes mellitus.

AIMS: Despite an increasing number of reports of ketoacidosis in populations with Type 2 diabetes mellitus, the pathophysiology of the ketoacidosis in these patients is unclear. We therefore tested the roles of three possible mechanisms: elevated stress hormones, increased free fatty acids (FFA), and suppressed insulin secretion. METHODS: Forty-six patients who presented to the Emergency Department with decompensated diabetes (serum glucose > 22.2 mmol/l and/or ketoacid concentrations > or = 5 mmol/l), had blood sampled prior to insulin therapy. Three groups of subjects were studied: ketosis-prone Type 2 diabetes (KPDM2, n = 13) with ketoacidosis, non-ketosis-prone subjects with Type 2 diabetes (DM2, n = 15), and ketotic Type 1 diabetes (n = 18). RESULTS: All three groups had similar mean plasma glucose concentrations. The degree of ketoacidosis (plasma ketoacids, bicarbonate and anion gap) in Type 1 and 2 subjects was similar. Mean levels of counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine), and FFA were not significantly different in DM2 and KPDM2 patients. In contrast, plasma C-peptide concentrations were approximately three-fold lower in KPDM2 vs. non-ketotic DM2 subjects (P = 0.0001). Type 1 ketotic subjects had significantly higher growth hormone (P = 0.024) and FFA (P < 0.002) and lower glucagon levels (P < 0.02) than DM2. CONCLUSIONS: At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia.     

Severe diabetic ketoacidosis: the need for large doses of insulin.

A 21-year-old female with Type 1 diabetes mellitus (DM) presented in ketoacidosis. She received intravenous normal saline and insulin at 6 U/h and 1.26% sodium bicarbonate solution. After the blood glucose had fallen to 9.5 mmol/l, the saline infusion was changed to 5% glucose solution and the insulin infusion rate to 2 to 3 U/h. The next day the patient became more drowsy (Glasgow coma scale 13/15, later falling to 4/15). Computed tomography (CT) scan suggested cerebral oedema and the patient was treated with dexamethasone and mannitol. She remained critically ill for 48 h, eventually making a full recovery. Insulin was given at rates of 8 to 14 U/h, with 10% or 20% glucose infusion to maintain the blood glucose above 5 mmol/l; despite this it was not until the fifth day that her serum bicarbonate became normal. Textbooks usually advise starting insulin at 6 U/h and reducing the infusion rate to 1-4 U/h when the blood glucose falls below a certain level. In this case, even with high rates of insulin infusion, it took 5 days before the patient's serum bicarbonate returned to normal. Thus, in severe diabetic ketoacidosis (DKA), protocols should advise that the insulin infusion be continued at high dose (4 to 6 U/h or more), with appropriate glucose infusion to prevent hypoglycaemia, until the serum bicarbonate is normal or nearly so.     

Bilateral optic atrophy following diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) can result in neuropathic abnormalities of the somatic and the autonomous nervous systems. We report the case of a 50-year-old man with Type 1 diabetes of 20-year duration who after severe DKA lost vision in his right eye and only retain partial vision in his left. This case demonstrates that optic neural tissue is vulnerable to haemodynamic and metabolic complications of DKA.     

Long-term risk of stroke in type 2 diabetes patients with diabetic ketoacidosis: A population-based,propensity score-matched,longitudinal follow-up study

AimTo investigate the long-term risk of stroke in type 2 diabetes (T2D) patients with previous episodes of diabetic ketoacidosis (DKA).MethodsThis retrospective nationwide population-based cohort study was conducted using Taiwan's National Health Insurance database. Claims data from 2000 to 2002 were extracted for 3572 T2D patients with DKA and 7144 controls matched for age, gender, diabetes complications severity index, frequency of clinical visits and baseline comorbidities. Patients with type 1 diabetes (T1D), identified by glucagon C-peptide stimulation or glutamic acid decarboxylase (GAD) antibody blood tests and possession of a catastrophic illness certificate were excluded. All patients were tracked until a new stroke diagnosis, death or the end of 2011.ResultsOf the 3572 selected patients, 270 with DKA and 404 of the 7144 controls were diagnosed with a new stroke, giving an incidence rate ratio (IRR) of 1.56 (95% CI: 1.34–1.82; P < 0.0001). DKA patients had a higher risk of ischaemic stroke than those without DKA (IRR: 1.62, 95% CI: 1.34–1.96; P < 0.0001), and DKA patients with hypertension and hyperlipidaemia were at even greater risk of stroke. Also, DKA patients were at particular risk for stroke during the first half-year following DKA diagnosis. After adjusting for patient characteristics and comorbidities, these patients were 1.55 times more likely to have a stroke than those without DKA (95% CI: 1.332–1.813, P < 0.0001).ConclusionT2D patients with previous DKA have a higher risk of stroke, especially ischaemic strokes.     

Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus.

AIMS: Limited data are available on determinants of diabetic neuropathy as its pathogenesis is multifactorial. Since homocysteine exhibits toxic effects on vascular endothelial cells, the association between homocysteine and the prevalence of neuropathy in Type 2 diabetes mellitus was investigated. METHODS: A total of 65 Type 2 diabetic patients were consecutively enrolled into the study. Neuropathy was diagnosed according to clinical symptoms, clinical examination, electrophysiological sensory testing and autonomic function testing. With regard to homocysteine-related parameters, plasma homocysteine, folate, vitamin B12, vitamin B6 and renal function (creatinine, ceratinine clearance, cystatin C) were measured, and the C677T polymorphism of the methylenetetrahydrofolate reductase gene was determined. RESULTS: Forty-three of the Type 2 diabetic patients were classified as suffering from neuropathy. Both patient groups were comparable with regard to demographic data, blood pressure, glucose metabolism, renal function and homocysteine-related vitamins. In contrast, homocysteine levels (P = 0.04) and the frequency of hyperhomocysteinemia (>or= 15 micromol/l) (P = 0.01) were significantly increased in neuropathic patients. In a logistic regression model with neuropathy as dependent variable, homocysteine (adjusted for creatinine, homocysteine-related vitamins, HbA1c and duration of diabetes) was the only significant variable associated with the prevalence of neuropathy (odds ratio for homocysteine per 5 micromol/l increase: 2.60 (95% confidence interval 1.07-6.33)). CONCLUSION: The data indicate that homocysteine is independently associated with the prevalence of diabetic neuropathy in a collective of Type 2 diabetic patients. A larger, prospective study would be desirable to clarify the role of homocysteine in the pathogenesis of diabetic neuropathy.     

Melatonin ameliorates SGLT2 inhibitor-induced diabetic ketoacidosis by inhibiting lipolysis and hepatic ketogenesis in type 2 diabetic mice

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective hypoglycemic agents that can induce glycosuria. However, there are increasing concerns that they might induce diabetic ketoacidosis. This study investigated the effect of melatonin on SGTL2i-induced ketoacidosis in insulin-deficient type 2 diabetic (T2D) mice. The SGLT2i dapagliflozin reduced blood glucose level and plasma insulin concentrations in T2D mice, but induced increases in the concentrations of plasma β-hydroxybutyrate, acetoacetate, and free fatty acid and a decrease in the concentration of plasma bicarbonate, resulting in ketoacidosis. Melatonin inhibited dapagliflozin-induced ketoacidosis without inducing any change in blood glucose level or plasma insulin concentration. In white adipose tissue, melatonin inhibited lipolysis and downregulated phosphorylation of PKA, HSL, and perilipin-1. In liver tissue, melatonin suppressed cellular cyclic AMP levels and downregulated phosphorylation of PKA, AMPK, and acetyl-CoA carboxylase (ACC). In addition, melatonin increased hepatic ACC activity, but decreased hepatic CPT1a activity and acetyl-CoA content. These effects of melatonin on lipolysis and hepatic ketogenesis were blocked by pretreatment with melatonin receptor antagonist or PKA activator. Collectively, these results suggest that melatonin can ameliorate SGLT2i-induced ketoacidosis by inhibiting lipolysis and hepatic ketogenesis though cyclic AMP/PKA signaling pathways in T2D mice. Thus, melatonin treatment may offer protection against SGLT2i-induced ketoacidosis.     

Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus.

AIMS: To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results. METHODS: We have investigated the role of two aldose reductase polymorphisms in four independent cohorts of cases and controls (two each with Type 1 and Type 2 diabetes) drawn from two ethnic populations, including 471 patients with nephropathy and 494 control diabetic patients without nephropathy. A C/T transition at position -106, and a (CA)n microsatellite marker 2.1 kb from the start site of the aldose reductase gene were genotyped in nephropathic patients and non-nephropathic controls from each cohort. RESULTS: Carriage of the -106 T allele was significantly associated with diabetic nephropathy in three of the four study groups. The Mantel-Haenszel combined odds ratio was 2.22 (95% CI 1.69, 2.94), P = 1.05 x 10(-8). We found no evidence for association of the microsatellite marker with nephropathy, despite moderate levels of disequilibrium between the two markers. Meta-analysis of published data yielded no evidence for association of the microsatellite marker with diabetic nephropathy in Type 2 diabetes, but varying degrees of association with diabetic nephropathy in Type 1 diabetes. CONCLUSIONS: Meta-analyses provide more convincing evidence of a role for the ALR2-106 marker than for the microsatellite marker in diabetic nephropathy (DN). More studies are now required to confirm these results and to establish whether the ALR2-106 polymorphism has a functional role in DN.     

Tuberculous meningitis associated with diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of type 1 diabetes mellitus. Infections are the leading cause of DKA, but trauma, myocardial infarction, or surgery may also precipitate this condition. In patients with DKA, although cerebral edema is the most common cause of neurological symptoms, other possibilities such as meningitis or encephalitis should also be considered. Herein, we present the case of an 8-year-old girl with DKA and tuberculous meningitis.     

Simultaneous pulmonary and cerebral oedema, and multiple CNS infarctions as complications of diabetic ketoacidosis: a case report.

We present a case of a 29-year-old woman with known Type 1 diabetes who presented with diabetic ketoacidosis (DKA). Despite appropriate treatment and initial improvement, 12 h after initiation of treatment she deteriorated rapidly and developed pulmonary oedema, cerebral oedema and multiple infarctions of the brain and cervical spinal cord. This resulted in spastic quadraparesis and she has remained wheelchair-bound. These complications of DKA are rare and unpredictable. In this case report we discuss the proposed aetiologies of these complications with reference to our case report and highlight the importance of vigilance for early signs of these complications during the treatment of all patients with DKA.     

Factors associated with discontinuing insulin therapy after diabetic ketoacidosis in adult diabetic patients.

AIMS: To assess the factors associated with successful discontinuation of insulin therapy after diabetic ketoacidosis (DKA) in adult patients. METHODS: Patients (>or= 18 years) attending the Endocrine and Metabolism Clinic at a major hospital in southern Taiwan were recruited. After recovery from the acute stage, those with no contraindications to oral antidiabetic agents, with adequate beta cell reserve, and with no antiglutamic acid decarboxylase (GAD) antibody were treated with oral agents. RESULTS: Sixty-six patients (38 males, 28 females, aged 18-76 years) were included, and 21 qualified for treatment with oral agents. These 21 patients were older at diagnosis of diabetes (45.5 +/- 14.0 vs. 40.0 +/- 13.8 years, P = 0.047), had shorter diabetes duration (median 0 vs. 5.5 months, P = 0.040), higher BMI (median 23.4 vs. 19.5 kg/m2, P < 0.001), higher serum osmolality during DKA (352.1 +/- 40.7 vs. 318.0 +/- 16.4 mmol/kg, P = 0.005), and lower insulin dose following recovery (median 0.49 vs. 0.83 unit/kg/d, P < 0.001) than those patients that had to continue insulin therapy. Thirteen patients (8 males, 5 females; 62%) successfully discontinued insulin for at least one year without recurrence of DKA. Multiple logistic regression analyses showed that BMI >or= 25 kg/m2 (adjusted relative risk (ARR) 8.85, 95% CI 1.05, 8.39), diabetes onset age >or= 40 years (ARR 8.08, 95% CI 1.16, 6.95), and undiagnosed diabetes before DKA (ARR 8.90, 95% CI 1.19, 7.51) were significant factors associated with successful discontinuation of insulin therapy. CONCLUSION: We identified three independent clinical factors associated with successful discontinuation of insulin therapy after DKA.     

Familial clustering of diabetic retinopathy in South Indian Type 2 diabetic patients.

AIM: The aim of the study was to determine whether there is familial clustering of diabetic retinopathy among South Indian Type 2 diabetic subjects. METHODS: During the period September 1991 to September 1997, 322 families with at least two diabetic siblings who were registered at our centre and had undergone a retinal examination were selected for the study.The sibling with the longest duration of diabetes was defined as the proband. The prevalence of retinopathy was compared between the siblings of probands with and without retinopathy. RESULTS: Diabetic retinopathy was diagnosed in 11.2% of the siblings of the probands without diabetic retinopathy and in 35.3% of the siblings of the probands with diabetic retinopathy (P < 0.0001). The increased prevalence of retinopathy among siblings of probands with retinopathy represented all grades of retinopathy, namely non-proliferative diabetic retinopathy with and without maculopathy and proliferative diabetic retinopathy, although the latter did not reach statistical significance due to the small numbers. Hypertension, metabolic control and the duration of diabetes among the probands did not affect the clustering of retinopathy. The odds ratio for retinopathy in the siblings of probands with retinopathy after adjusting for age, glycosylated haemoglobin, duration of diabetes, proteinuria and other confounding variables was 3.37(95% confidence interval 1.56-7.29, P = 0.002). CONCLUSIONS: Familial clustering of diabetic retinopathy was three times higher in siblings of Type 2 diabetic subjects with diabetic retinopathy.     

A rare case of diabetic ketoacidosis presenting with severe hypertriglyceridemia requiring plasmapheresis in an adult with type-2 diabetes mellitus: Case report

Introduction:Severe hypertriglyceridemia (HTG) is a rare complication of insulin resistance. Its presentation with diabetic ketoacidosis (DKA) has been reported in a few cases, where most patients have type-1 diabetes mellitus (DM). Our case represents a unique presentation of DKA associated with severe HTG above 10,000 mg/dL in an adult with type-2 DM.Patient concerns and diagnosis:Case Report: A 51-year-old man with no prior illnesses presented to the emergency department with abdominal pain and nausea. He was found to have DKA with a blood glucose level of 337 mg/dL, pH of 7.17, beta-hydroxybutyrate of 7.93 mmol/L, and anion gap of 20 mmol/L. His triglyceride levels were >10,000 mg/dL. His serum was found to be lipemic. Computerized tomography scan of the abdomen demonstrated mild acute pancreatitis. Negative GAD65 antibodies supported the diagnosis of type-2 DM.Interventions and outcomes:Endocrinology was consulted and one cycle of albumin-bound plasmapheresis was administered. This therapy significantly improved his HTG. DKA gradually resolved with insulin therapy as well. He was discharged home with endocrinology follow-up.Conclusion:This unique case highlights an uncommon but critical consequence of uncontrolled DM. It brings forth the possibility of severe HTG presenting as a complication of uncontrolled type-2 DM. Severe HTG commonly presents with acute pancreatitis, which can be debilitating if not managed promptly. Most patients with this presentation are managed with insulin infusion. The use of plasmapheresis for management of severe HTG has not been well studied. Our case supports the use of plasmapheresis as an effective and rapid treatment for severe HTG.     

Type 2 diabetes mellitus in UK children--an emerging problem.

AIMS: Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester. METHODS: Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma. RESULTS: Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin. CONCLUSIONS: These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.     

Positive troponin in diabetic ketoacidosis without evident acute coronary syndrome predicts adverse cardiac events

BACKGROUND: Elevated troponin I has been associated with increased mortality in critically ill patients without acute coronary syndrome (ACS). However, the prognostic significance of troponin elevation in patients with diabetic ketoacidosis (DKA) without evident ACS has not been studied. METHODS: Retrospective study of all patients admitted to a U.S. tertiary center between 01/98 and 12/00 with DKA and had troponin I level measured. Patients with evidence of ACS or who met the American College of Cardiology/European Society of Cardiology (ACC/ESC) definition for myocardial infarction were excluded. Baseline characteristics, cardiac evaluation and 2 year major adverse coronary event (MACE) rate were compared between patients with positive and negative troponin. RESULTS: Ninety-six patients fulfilled the inclusion criteria of this study, 26 had positive troponin. There were no differences in baseline characteristics between the two groups. After a 2 year follow-up, there was significantly increased mortality in patients with elevated troponin (50.0% versus 27.1%, hazard-ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.8, p = 0.02). Patients with elevated troponin also had significantly increased MACE rate at 2 years (50.0% versus 28.6%, HR 2.6, 95% CI 1.3-5.3, p = 0.007) driven primarily by mortality. Using Cox Proportional Hazard Analysis, elevated troponin was a predictor of increased MACE after adjusting for confounding variables. (Adjusted HR 2.3, 95% CI 1.1-4.6, p = 0.02) CONCLUSIONS: Elevated troponin I in diabetic patients admitted with DKA identifies a group at very high risk for future cardiac events and mortality. Whether cardiac risk stratification of these patients will improve long term outcome remains to be studied.     

Factors affecting diabetes knowledge in Type 2 diabetic veterans

Aims/hypothesis To describe the clinical, psychological and social factors affecting diabetes knowledge of veterans with established Type 2 diabetes.Methods We conducted an observational study of 284 insulin-treated veterans with stable Type 2 diabetes. All subjects completed the University of Michigan Diabetes Research and Training Centre Knowledge Test, the Diabetes Care Profile, the Mini-Mental State Examination, the Geriatric Depression Scale, and the Diabetes Family Behaviour Checklist. Stepwise multiple linear regression was used to develop a model for the diabetes knowledge score based upon clinical and psychosocial variables.Results One hundred eighty subjects were evaluated in a derivation set. The mean age ± SD was 65.4±9.6 years, 94% were men, and 36% were members of a minority group. Performance on the diabetes knowledge test was poor (64.9±15.3% correct). Self-perceived understanding of all management objectives explained only 6% of the variance in the knowledge scores. Multivariate analysis showed that age, years of schooling, duration of treatment, cognitive function, sex, and level of depression were independent determinants of the knowledge score. When the model was applied to 104 subjects in a validation set, there was a strong correlation between observed and predicted scores (r=0.537; p<0.001).Conclusions/interpretation Stable, insulin-treated veterans have major deficiencies in diabetes knowledge that could impair their ability to provide self-care. A multivariate model comprised of demographic variables and psychosocial profiling can identify patients who have limited diabetes knowledge and be used to assess individual barriers to ongoing diabetes education.Abbreviations DOVES Diabetes Outcomes in Veterans Study - VA Veterans Affairs - ADA American Diabetes Association