Insulin infusion responses in diabetic ketoacidosis alone and with a mixed hypochloremic alkalosis

AimsAlthough diabetic ketoacidosis (DKA) commonly presents as a pure diabetic ketoacidosis (PDKA), up to 30% of cases may be associated with a mixed hypochloremic metabolic alkalosis (HMA). It is unknown whether there is a difference in treatment outcomes between these two entities. We evaluated an insulin infusion protocol (IIP), previously validated for hyperglycemia management in ICU's, for the management of PDKA and HMA.Materials and methodsA retrospective case series/cohort study of 41 DKA admissions was further characterized as having PDKA or HMA. HMA was defined in those having an elevated delta-delta gradient (ΔAG-ΔHCO3) ≥ 5 mmol/L and base excess chloride (BE_Cl) > 2.7 mmol/L. The main outcome measures were times to recovery of glucose levels to ≤250 mg/dL and of anion gap to ≤12 mmol/L.ResultsThe initial serum glucose was 553 ± 265 mg/dL, serum bicarbonate of 8.8 ± 5.1 mmol/L, and venous pH 7.13 ± 0.2). Recovery of glucose occurred in 5 h: 25 min (±3 h:39min), and for anion gap in 11 h:25 min (±6 h:56min). HMA compared with PDKA had a delayed recovery of serum glucose (7 h: 23min ± 3 h: 35min vs. 4 h: 31min ± 3:h:21min, p = 0.017), which was due to the higher initial level of glucose (p = 0.02) rather than level of BE_Cl (p = 0.17). There was no difference in time to anion gap closure between the PDKA and HMA.ConclusionsCorrection of hyperglycemia and acidosis in PDKA as well as in HMA was managed through the IIP. The simultaneous fluid and electrolyte management corrected the hypochloremic alkalosis.     

Cétose ou acidocétose diabétique euglycémique chez des patients diabétiques de type 2 traités par inhibiteurs du SGLT2 : une série de cas cliniques en Belgique

IntroductionSodium-glucose cotransporter type 2 inhibitors (SGLT2i) are new therapeutic agents that improves the management of type 2 diabetes. Clinical trial results for SGLT2i have shown a reduction in blood glucose levels and a decrease in significant cardiovascular and renal complications related to diabetes. However, rare adverse events such as diabetic ketoacidosis have been reported in these clinical trials and in “real life”. These ketoacidosis were atypical because the hyperglycemia was less severe than in traditional acute diabetes, hence the name of “euglycemic” ketoacidosis. We detail a series of local cases associated with the use of SGLT2i in type 2 diabetic patients.MethodsThis was a retrospective consecutive case study, with a review of medical records from 2016 to 2019. We identified 7 single episodes of “euglycemic” ketoacidosis associated with SGLT2i use in individuals with type 2 diabetes.ResultsSeven cases of type 2 diabetic individuals (M/F: 5/2) aged from 51 to 74 years old were analysed. All had symptoms of hyperketonemia (fruity smelling breath, nausea or lack of appetite) and an increase level of capillary β-hydroxybutyric acid despite a glycaemia between 112 and 280 mg/dL. The risk factors for ketoacidosis identified in these patients were: prolonged fasting, infection, dehydration and significantly decreased in insulin secretory function (according to the HOMA model), revealing endogenous insulinopenia before ketoacidosis.ConclusionThe increasing use of SGLT2i in individuals with type 2 diabetes is likely to increase the number of ketoacidosis cases. It is essential to recognise this complication and prevent it according to each patient's risk factors.     

Application of the Sampson equation to estimate LDL-C in children: Comparison with LDL direct measurement and Friedewald equation in the BLIP study

Background and aimsIn epidemiological trials and in clinical practices, it is relevant to have affordable and reliable methods to measure the main lipid cardiovascular risk factors, and in particular low-density lipoprotein cholesterol (LDL-C) plasma level. In this context, we aimed to compare the reliability of the Friedewald's (LDL-Cf) and Sampson's (LDL-Cs) equations with the LDL-value dosed by a validated dosage method (LDL-Cd) in a large cohort of children.Methods and resultsWe considered the lipid values of 145 infants, 278 preschoolers, 810 scholar children, and 1372 adolescents (Total N. 2605, 1291 males, 1314 females), with mean total cholesterol (TC) = 169.8 ± 39.7 mg/dL, HDL-Cholesterol = 50.8 ± 12.7 mg/dL, non HDL-Cholesterol = 118.9 ± 35.9 mg/dL, Triglycerides (TG) = 90.3 ± 77.9 mg/dL, LDL-Cd = 106.2 ± 29.9 mg/dL, LDL-Cf = 100.9 ± 33.8 mg/dL, and LDL-Cs = 102.2 ± 33.4 mg/dL. Comparing the distance to the LDL-Cd, Friedewald's equation mildly but significantly underestimated in infants (3.4 ± 5.3 mg/dL), preschoolers (1.5 ± 7.1 mg/dL). Children (1.2 ± 2.2 mg/dL) and adolescents (1.1 ± 5.9 mg/dL) compared to Sampson's equation (all comparisons, p < 0.001).ConclusionsOur analysis, being carried out on a large population sample, shows that Sampson's equation is more reliable than Friedewald's one at each considered age class and even for extreme TG values.     

Associative factors of existing fragility fractures among elderly medical inpatients: A hospital-based study

BackgroundFragility fractures are important in public health because of the increase of morbidity, mortality and cost worldwide. Most fragility fractures occur in patients who have no osteoporosis, but the association with frailty syndrome and cerebrovascular disease is stronger. The main purpose of this study was to evaluate comorbid conditions associated with elderly medical inpatients admitted to the Geriatric Evaluation and Management Unit with existing fragility fractures.MethodsThis was a retrospective study screening all medical records of patients admitted to the Geriatric Evaluation and Management Unit of a tertiary medical center from March, 2010 to April, 2011. Patients who had bone mineral density examinations of the hips in the past 5 years were enrolled. Pathological fractures or fractures caused by major trauma were excluded. Demographic characteristics, such as age, sex, height, weight, body mass index, bone mineral density, underlying comorbidity, blood biochemistry, and fracture sites were carefully recorded.ResultsOverall, 169 patients (mean age: 84 years, range: 66–96 years; 62.1% male) were enrolled, and fragility fractures were identified in 130 patients, including 115 vertebral fractures, 12 hip fractures and three pelvic fractures. Patients with existing fragility fractures were significantly lower in T score (?2.33 ± 1.10 vs. ?1.87 ± 1.23, p = 0.030), serum albumin (3.6 ± 0.4 mg/dL vs. 3.9 ± 0.4 mg/dL, p = 0.003), total protein (6.4 ± 0.9 mg/dL vs. 6.9 ± 0.7 mg/dL, p = 0.007), blood urea nitrogen (20.4 ± 11.6 mg/dL vs. 26.3 ± 13.9 mg/dL, p = 0.014), and creatinine (1.0 ± 0.6 mg/dL vs. 1.4 ± 0.7 mg/dL, p < 0.001), but not in bone mineral density (0.59 ± 0.25 g/cm³ vs. 0.66 ± 0.16 g/cm³, p = 0.120) and diagnosis of osteoporosis (41.5% vs. 25.6%, p = 0.073). A multivariate logistic regression model showed that serum levels of albumin<3.5 mg/dL (odds ratio: 4.6, 95% confidence interval: 1.1–18.2, p = 0.032) and creatinine <0.8 mg/dL (odds ratio: 10.8, 95% confidence interval: 1.2–97.3, p = 0.033) were significantly associated with existing fragility fractures.ConclusionFor medical patients, fragility fractures were significantly associated with low serum levels of albumin and creatinine, which may be suggestive of malnutrition and low muscle mass. A further prospective study is needed to clarify the sequential effect of fragility fracture, malnutrition and sarcopenia.     

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.     

Aminoaciduria and metabolic dysregulation during diabetic ketoacidosis: Results from the diabetic kidney alarm (DKA) study

ObjectiveWe examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D).MethodsUrine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, blood glucose 451 ± 163 mg/dL) at 3 time points: 0–8 h and 12–24 h after starting an insulin infusion, and 3 months after hospital discharge. Mixed-effects models evaluated the changes in amino acids and other metabolites in the urine.ResultsConcentrations of urine histidine, threonine, tryptophan, and leucine per creatinine were highest at 0–8 h (148.8 ± 23.5, 59.5 ± 12.3, 15.4 ± 1.4, and 24.5 ± 2.4% of urine creatinine, respectively), and significantly decreased over 3 months (p = 0.028, p = 0.027, p = 0.019, and p < 0.0001, respectively). Urine histidine, threonine, tryptophan, and leucine per urine creatinine decreased by 10.6 ± 19.2, 0.7 ± 0.9, 1.3 ± 0.9, and 0.5 ± 0.3-fold, respectively, between 0 and 8 h and 3 months.ConclusionsIn our study, DKA was associated with profound aminoaciduria, suggestive of proximal tubular dysfunction analogous to Fanconi syndrome.     

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study

Background and aimsCoronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD.Methods and resultsThis was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131–3.136]), C-reactive protein (1.046 [1.020–1.073]), blood pressure >140/90 mmHg (2.686 [1.506–4.791]), fibrates (2.032 [1.160–3.562]), calcium channel blockers (2.082 [1.158–3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240–4.721]), heart failure (2.139 [1.032–4.433]), LDL-C >70 mg/dL (4.594 [1.401–15.069]), and diuretics (3.328 [1.677–6.605]) were associated with cardiovascular mortality.ConclusionsThe composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.     

Kawasaki Disease Shock Syndrome vs Classical Kawasaki Disease: A Meta-analysis and Comparison With SARS-CoV-2 Multisystem Inflammatory Syndrome

BackgroundThe emergence of increasing reports worldwide of a severe inflammatory process and shock in pediatric patients resembling Kawasaki disease (KD)—and, more specifically, Kawasaki disease shock syndrome (KDSS)—prompted us to explore KDSS in a preamble of a systematic comparison between the 2 conditions.MethodsWe completed a systematic review of KDSS and performed a meta-analysis comparison between reported KDSS cases and KD controls.ResultsA total of 10 case-control series were included in the meta-analysis. Patients with KDSS were older (38.4 ± 30.6 vs 21.9 ± 19.5 months; P < 0.001) compared with standard KD with equal sex distribution and completeness of clinical diagnostic criteria. KDSS present higher C-reactive protein (59.4 ± 29.2 mg/dL vs 20.8 ± 14.8 mg/dL; P < 0.001), lower albumin (2.7 ± 0.5 g/dL vs 3.3 ± 0.5 g/dL; P < 0.01), and lower platelets (255 ± 149 109/L vs 394 ± 132 109/L; P < 0.001) but only borderline higher white blood cells (P = 0.06). Differences in alanine transaminase, aspartate aminotransferase, and erythrocyte sedimentation rate were nonsignificant. The odds of intravenous immunoglobulin resistance (44.4% vs 9.6%; (P < 0.001) and the hospital length of stay (10.9 ± 5.8 vs 5.0 ± 3.0 days; P < 0.001) were higher in KDSS, as were the odds of coronary-artery abnormalities (33.9% vs 8.6%; P < 0.001).ConclusionsThis first meta-analysis on KDSS vs KD represents a basis for future works on KDSS and opens the opportunity for future multicentre studies in the search of causal relationships between presenting elements and the eventual complications of KDSS. The similarities between SARS-CoV-2 multisystem inflammatory syndrome in children and KDSS open new horizons to the understanding of the etiology and pathophysiology related to KDSS.     

Starvation-induced True Diabetic Euglycemic Ketoacidosis in Severe Depression

True euglycemic diabetic ketoacidosis [blood glucose <200 mg/dl (11.1 mmol/l)] is relatively uncommon and in type 1 diabetes can be caused by starvation of any cause in conjunction with an intercurrent illness. We report a case of euglycemic diabetic ketoacidosis precipitated by starvation resulting from severe depression in a patient with type 1 diabetes. He was acidotic with ketonuria, but his blood glucose was only 105 mg/dl (5.8 mmol/l). He was rehydrated, the acidosis was corrected, and his depression was later treated. This case involves the complex interplay among type 1 diabetes, depression, ketoacidosis, and starvation physiology resulting in glucose concentrations in keeping with euglycemic diabetic ketoacidosis. The case also highlights that even in the absence of hyperglycemia, acid/base status should be assessed in an ill patient with diabetes, and in cases of euglycemic diabetic ketoacidosis, the diagnosis of depression should be considered as a cause for suppressed appetite and anorexia.     

Impact of low-starch high-fiber pasta on postprandial blood glucose

Background and aimsAlmost all of the energy in noodle dishes is derived from carbohydrates, particularly starch. Recently, we invented a pasta with reduced starch content to about 50% and increased dietary fiber content, designated low-starch high-fiber pasta (LSHFP). In this study, we investigated the ingestion of LSHFP on the postprandial glucose response as a breakfast meal.Methods and resultThis was a randomized, single-blinded, crossover study. The postprandial glucose area under the curve for 4 h (4h-gluAUC), as the primary outcome, and the extent of postprandial glucose elevation (maxΔBG) were evaluated using a continuous glucose monitoring system in healthy volunteers and patients with type 2 diabetes (T2DM) after intake of LSHFP, standard pasta (SP), and rice. The amount of total carbohydrate was matched between LSHFP and SP. Ten individuals with T2DM and 10 individuals who did not have T2DM and were otherwise healthy were enrolled in this crossover study. The 4h-gluAUC for LSHFP (137.6 ± 42.2 mg/dL?h) was significantly smaller than the 4h-gluAUC for rice (201.7 ± 38.7 mg/dL?h) (p = 0.001) and SP (178.5 ± 59.2 mg/dL?h) (p = 0.020). The maxΔBG for rice (118.6 ± 24.2 mg/dL) was significantly higher than those for SP (87.5 ± 19.9 mg/dL) (p < 0.001) and LSHFP (72.7 ± 26.2 mg/dL) (p = 0.001), while the maxΔBG for LSHFP (p = 0.047) was significantly lower than that for SP, in T2DM patients as well as in healthy participants.ConclusionsThis study demonstrated that LSHFP can reduce postprandial glucose elevation compared with SP in both healthy participants and patients with T2DM.     

Evaluation of the effects of glucose on osmolal gap using freezing point depression and vapor pressure methods

The measurement of serum osmolality, and the calculation of osmolal gap (OG) from a calculated osmolality are widely used in clinical and emergency medicine. In this study, the possible effects of blood glucose on OG were investigated by freezing point depression and vapor pressure methods. The concentrations of sodium, glucose, blood urea nitrogen and osmolalities of 2640 samples were measured. There were two methods for calculating serum osmolality: freezing point depression method (n = 2399) and vapor pressure method (n = 241). The OG was positively associated with glucose in glucose 110–450 mg/dL (r = 0.191, p < 0.001) and glucose > 450 mg/dL (r = 0.372, p < 0.001), but not in glucose < 110 mg/dL (r = 0.017, p = 0.711) in freezing point depression method. However, OG had no correlation with glucose regardless of glucose level in vapor pressure method. In freezing point depression method, compared with the groups of glucose <110 and 110–450 mg/dL, the group with glucose >450 mg/dL had higher OG (p < 0.001) and higher prevalence of OG > 10 mOsm/Kg H₂O (p < 0.001). Our study demonstrated that OG is impacted by increasing blood glucose concentration using freezing point depression method, special attention should be made to blood glucose concentrations when using freezing point depression method to determine OG.     

Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus

Background and aimsMonocyte chemoattractant protein-1 (MCP-1) and cathepsin-D are progressively raised in type 2 diabetes mellitus (T2DM) with both non proliferative and proliferative retinal disease. This study aimed to evaluate the effect of antidiabetic medications on MCP-1 and cathepsin-D.Methods60 patients of T2DM without retinopathy and 60 of diabetic retinopathy were enrolled to receive metformin (500 mg–1000 mg) combined with either glimepiride (1 mg–2 mg) or insulin. The effect of antidiabetic medications on serum MCP-1 and cathepsin-D was assessed.ResultsMean MCP-1 (pg/ml) and cathepsin-D (ng/ml) levels were significantly lower in patients of T2DM with and without retinopathy treated with metformin + insulin (468.52 ± 272.84 vs 234.30 ± 180.58; p < 0.01 and 460.15 ± 128.52 vs 517.33 ± 213.49; p = 0.214) as compared to patients treated with metformin + glimepiride (1434.02 ± 105.27 vs 1256.27 ± 76.76; p < 0.01 and 1689.36 ± 752.57 vs 919.69 ± 675.05; p = < 0.01). No significant correlation of MCP-1 and cathepsin-D with HbA1c, fasting and post prandial blood glucose were found.ConclusionPatients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy. (CTRI/2018/05/013601).     

Lipoprotein (a), metabolic syndrome and coronary calcium score in a large occupational cohort

Background and aimsWhether lipoprotein (a) [Lp(a)] concentration is associated with metabolic syndrome (MetS) and pre-clinical atherosclerosis in different ethnic groups is uncertain. The association between Lp(a), MetS and a measure of pre-clinical atherosclerosis was studied in a large Asian cohort.Methods and resultsData were analyzed from a South Korean occupational cohort who underwent a cardiac computed tomography (CT) estimation of CAC score and measurements of cardiovascular risk factors (n = 14,583 people). The key exposure was an Lp(a) concentration in the top quartile (>38.64 mg/dL)) with a CAC score >0 as the outcome variable and measure of pre-clinical atherosclerosis. Logistic regression was used to describe the associations. 1462 participants had a CAC score >0. In the lowest Lp(a) quartile (<11.29 mg/dL), 25.8% had MetS, compared with 16.1% in the highest Lp(a) quartile (>38.64 mg/dL (p < 0.001). MetS, and component features, were inversely related to Lp(a) concentration (all p < 0.0001). In the highest Lp(a) quartile group, there was an association between Lp(a) and CAC score >0 in men (OR 1.21[1.05, 1.40], p = 0.008), and women (OR 1.62[1.03, 2.55], p = 0.038), after adjustment for age, sex, lipid lowering therapy, and multiple cardiovascular risk factors. There was no evidence of an interaction between highest quartile Lp(a) and either high LDLc (>147 mg/dL) (p = 0.99), or MetS (p = 0.84) on the association with CAC score >0.ConclusionLp(a) levels are inversely related to MetS and its components. There was a robust association between Lp(a) concentration >38.6 mg/dL and marker of early atherosclerosis in both men and women, regardless of LDLc, level MetS or other cardiovascular risk factors.     

Changes in serum phosphate during treatment of diabetic ketoacidosis: predictive significance of severity of acidosis on presentation

Changes in serum phosphate during diabetic ketoacidosis (DKA) treatment are not well characterised, although it is known that serum phosphate falls with treatment. We sought to define the nature of these changes and whether the severity of acidosis on admission influenced the severity of subsequent hypophosphataemia. We retrospectively reviewed data on all patients with confirmed DKA presenting to our unit between 2007 and 2010 inclusive. Forty‐three patients with 64 episodes of DKA were evaluated. At presentation, 62.5% of patient episodes were hyperphosphataemic. Initial serum phosphate in all patient episodes correlated significantly with the initial serum creatinine (r = 0.694, P < 0.01) and the initial blood glucose (r = 0.593, P < 0.01). Serum phosphate fell during the course of treatment in all episodes (mean absolute fall 1.28 ± 0.77 (SEM) mmol/L). The mean nadir phosphate was 0.58 ± 0.19 mmol/L. Ninety per cent of nadir phosphate levels were hypophosphataemic (<0.8 mmol/L), and 11% were severely hypophosphataemic (<0.32 mmol/L). Mean initial bicarbonate differed significantly between those with nadir phosphates <0.5 mmol/L (9.26 ± 4.55) and those with nadir phosphates >0.5 mmol/L (13.0 ± 4.59, P = 0.0031). Similar significant bicarbonate differences were noted between those with nadir phosphates less than and more than 0.32 mmol/L respectively (7.42 ± 2.44 and 12.2 ± 4.87, P < 0.01). The initial hyperphosphataemia is reflective of intravascular volume depletion and pre‐renal renal impairment. The severity of subsequent hypophosphataemia can be predicted by the degree of metabolic acidosis on presentation. As profound hypophosphataemia can be associated with serious complications, clinicians should recognise the likelihood of this biochemical derangement in those DKA patients presenting with profound acidosis.     

Effect of Atorvastatin on blood ketone levels and glycemic control in patients with type 2 diabetes mellitus: A single arm pilot study

Background and aimsCholesterol and ketone bodies are synthesized in liver from a common precursor acetyl coenzyme A (acetyl-CoA). Statins by inhibiting cholesterol synthesis may lead to accumulation of acetyl-CoA in hepatocytes and its diversion towards ketogenesis. Ketone bodies may act as alternative energy source thus sparing blood glucose and contributing to hyperglycemia. The present study aims to assess the effect of Atorvastatin therapy on blood ketone levels and glycemic control in patients with T2DM.MethodsStudy included 24 statin naïve subjects with T2DM. They were prescribed tablet Atorvastatin at dose of 10 mg once daily at bedtime. Ongoing anti-diabetic medications were not changed. Estimation of blood ketones, urine ketones, fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated hemoglobin (HbA1c) and lipid parameters was carried out at baseline and at 3 months after starting Atorvastatin.ResultsThere was moderate but significant increase in blood ketones (0.16 ± 0.08 mmol/L vs. 0.26 ± 0.07 mmol/L; p-value = 0.0000), FPG (133.8 ± 17.91 mg/dL vs. 143.3 ± 22.99 mg/dL; p-value = 0.0016) and PPG (193.0 ± 36.54 mg/dL vs. 211.0 ± 49.51 mg/dL; p-value = 0.0344) after 3 months of Atorvastatin therapy. This was associated with significant reduction in serum total cholesterol and low density lipoprotein cholesterol.ConclusionThree months therapy with Atorvastatin at the dose of 10 mg once daily at bedtime in patients with T2DM resulted in moderate rise in blood ketone levels, FPG and PPG in addition to improvement in lipid parameters.     

Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography

AimTo evaluate the effect of specific lipoprotein(a) [Lp(a)] apheresis on coronary atherosclerosis progression in coronary heart disease (CHD) patients with elevated Lp(a) levels.MethodsA total of 30 subjects (mean age 53.5 ± 8.3 years, 70% male) with CHD verified by angiography, Lp(a) > 50 mg/dL, and low density lipoprotein cholesterol (LDL-C) ≤ 2.5 mmol/L on chronic statin treatment were prospectively evaluated for 18 months. Patients were allocated to receive specific Lp(a) apheresis, which was carried out weekly with Lp(a) Lipopak^® columns (POCARD Ltd., Russia) (n = 15), or atorvastatin only (n = 15). Blinded quantitative coronary angiography analyses of percent diameter stenosis and minimal lumen diameter (MLD) were performed at baseline and after the 18-month treatment period.ResultsBy the single specific Lp(a) apheresis procedure, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean Lp(a)-corrected LDL-C decreased by 7% to a mean of 1.4 mmol/L. Median percent diameter stenosis was reduced by ?2.0 (95% confidence interval [CI], ?5.0–0.0) with apheresis (p < 0.01 in comparison with baseline), and increased by 3.5 (0.0–6.9) with atorvastatin (p < 0.001 between the groups). The effect on MLD was more favorable with apheresis than with atorvastatin: 0.20 ± 0.39 mm, as compared with 0.01 ± 0.34 mm, p = 0.04. Lp(a) apheresis had greater efficacy regarding the amount of regressed/stabilized coronary segments than atorvastatin alone in the majority of patients (chi-square test 13.61, p < 0.005).ConclusionSpecific Lp(a) apheresis for 18 months produced coronary atherosclerosis regression in stable CHD patients with high Lp(a) levels and reached LDL-C goals.     

The role of plasma fibrinogen,D-dimer and fibrinogen degradation products in diagnosis and disease activity in patients with ankylosing spondylitis

Aim of the workTo evaluate the role of coagulation-related markers such as plasma fibrinogen, D-dimer and fibrinogen degradation product (FDP) in ankylosing spondylitis (AS) patients and their relationship with disease activity.Patients and methodsData were collected from 210 AS patients and 204 age and gender matched healthy controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to divide AS patients into active (≥4) and inactive (score < 4) groups.ResultsThe mean age of the patients was 35.3 ± 16.3 years. They were 156 males and 54 females (M:F 2.9:1) and had a disease duration of 9.4 ± 7.2 years. The mean fibrinogen, D-dimer and FDP were significantly increased in the patients (375.4 ± 125.01 mg/dl, 2874.8 ± 1884.6 ug/l and 18.3 ± 11.3 mg/l) compared to the control (276.7 ± 71.9 mg/dl, 913.3 ± 540.6 ug/l and 3.01 ± 1.2 mg/l respectively; p < 0.001 each). Plasma fibrinogen, D-dimer and FDP increased in active compared to inactive patients (p < 0.001) and were significantly associated with BASDAI (p < 0.001). The optimal cut-off value of plasma fibrinogen, D-dimer and FDP for the diagnosis of AS were >288 mg/dl, >472 ug/l and >1.44 mg/l while to discriminate active from inactive the values were 393 mg/dl, 1228 μg/L and 1.82 mg/L, respectively. Logistic regression analysis showed that D-dimer is an independent predictor for AS disease activity (OR = 2.85, 95%CI: (1.85--4.43), p < 0.001).ConclusionFibrinogen, D-dimer and FDP increased in AS patients and significantly correlated with disease activity. D-dimer may play a role as a novel inflammatory parameter to predict disease activity in AS patients.     

Insulin increases serum leptin concentrations in children and adolescents with newly diagnosed Type I diabetes mellitus with and without ketoacidosis

Abstract Aims/hypothesis. The aims of this study were to analyse the changes of serum leptin in newly diagnosed children and adolescents with Type I (insulin-dependent) diabetes mellitus after insulin treatment and to examine the possible impact of ketoacidosis on these changes. Methods. Baseline serum leptin concentrations were measured in 28 newly diagnosed Type I diabetic patients [age 8.75 ± 4.05 years (means ± SD); BMI 15.79 ± 2.47 kg/m²; HbA_{1 c} 11.3 ± 1.9 %] with (n = 18) and without (n = 10) ketoacidosis before commencement of insulin treatment, at the time of diagnosis. Thereafter, during a 4-day course of continuous intravenous insulin injection to gain and maintain euglycaemia, serum leptin concentrations were assessed. Results. Baseline serum leptin concentrations, adjusted to age, BMI, sex and pubertal stage, differed among these patients. There was, however, an increase of leptin in all subjects from 1.37 ± 0.56 ng/ml (mean ± SD) up to 2.97 ± 1.52 ng/ml by 117 % (p < 0.0001) after insulin therapy. On average, peak serum leptin concentration was obtained after 42 h of insulin treatment. Further, there was no difference in the mean increase of serum leptin concentrations in the two groups, namely with and without ketoadicosis, of insulin-dependent diabetic children and adolescents. In addition, there was no correlation between serum leptin concentrations and correction of ketoacidosis during insulin treatment. Conclusions/interpretation. Insulin increases serum leptin, within 1 day, in children and adolescents with newly diagnosed Type I diabetes. Ketoacidosis does not influence this interaction between insulin and leptin. [Diabetologia (1999) 42: 1067–1070] Received: 12 April 1999 and in revised form: 20 May 1999     

Long-term efficacy and safety of anti-hyperglycaemic agents in new-onset diabetes after transplant: Results from outpatient-based 1-year follow-up and a brief review of treatment options

Background and aimsEvaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up.MethodsWe collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included.ResultsIn ninety-five patients’ (Male = 65), mean decrease at 1-year from baseline in FPG (185.01 ± 62.11 mg/dL), PPG (293.21 ± 85.23 mg/dL) and HbA1c (8.48 ± 1.08%) was 67.09, 126.11 and 1.4 respectively (p < 0.0001). At 1-year, mean HbA1c was 7.08 ± 0.38%, ninety-one patients achieving HbA1c ≤ 7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56 ± 0.62 mg/dL and 53.95 ± 16.10 mL/min/1.73 m² respectively.ConclusionsSignificant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.     

Disagreement between capillary blood glucose and flash glucose monitoring sensor can lead to inadequate treatment adjustments during pregnancy

ObjectiveContinuous glucose monitoring tends to replace capillary blood glucose (CBG) self-monitoring. Our aim was to determine the agreement between CBG and a flash glucose monitoring system (Flash-GMS) in treatment decision-making during pregnancy.Research Design and MethodsInsulin-treated women with either type 1 (n = 25), type 2 (n = 4) or gestational diabetes (n = 4) were included. A Flash-GMS sensor was applied for 14 days. Women scanned the sensor whenever they monitored their CBG. The primary endpoint was the proportion of discordant therapeutic decisions they would have made based on Flash-GMS rather than CBG results. Glucose averages, mean absolute difference (MAD), mean absolute relative difference (MARD) and Flash-GMS accuracy were also estimated.ResultsData for forty 14-day periods were available. Preprandial Flash-GMS and CBG values were 93 ± 42 mg/dL and 105 ± 45 mg/dL, respectively (P < 10⁻⁴), and 2-h postprandial (PP) values were 106 ± 45 mg/dL and 119 ± 47 mg/dL, respectively (P < 10⁻⁴). MAD was 14 ± 22 mg/dL preprandial and 15 ± 24 mg/dL 2-h PP; MARD was 19%; and 99% of glucose value pairs were within the clinically acceptable A and B zones of the Parkes error grid. Concordance rate for therapeutic decision-making was 80–85% according to ADA targets and 65–75% according to a pragmatic threshold. At different time points of the day, 83–92% of discordant results were due to Flash-GMS values being lower than their corresponding CBG values.ConclusionFlash-GMS tends to give lower estimates than CBG. Thus, in cases requiring therapeutic changes to treat or prevent hypo- or hyperglycaemia, 25–35% of choices would have been divergent if based on Flash-GMS rather than CBG.