Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study.

BACKGROUND: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM. METHODS: We linked 659 906 individuals born in Denmark 1990-2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981-2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders. RESULTS: Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35-1.42; grandparents: 1.14, 1.13-1.15; and aunts/uncles: 1.19, 1.16-1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08-1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa. CONCLUSIONS: Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.

Alstrom's Syndrome: An Experience of Tertiary Care Center.

Alstrom's syndrome (AS) is an autosomal recessively inherited multisystemic disorder that falls under the umbrella of ciliopathy. It is characterized by poor vision, hearing impairment, cardiomyopathy, childhood obesity, diabetes mellitus type 2, dyslipidemia, pulmonary, hepatic, and renal failure besides systemic fibrosis. Biallelic pathogenic variants in ALMS1 gene cause AS. Retrospective study (1990-2017) included 12 Saudi patients with AS based on their phenotype, biochemical markers, and genotype. The study was approved by Fisal Specialist Hospital and Research Centre, Riyadh (RAC number 2131129) on October 2, 2012. This study showed clinical and genetic heterogeneity; six patients showed a founder mutation (IVS18-2A > T in exon 19), whereas six others showed private mutations. AS in Saudi Arabia is underdiagnosed probably because of its variable clinical manifestations. We report 12 Saudi patients with AS to enhance the awareness about this syndrome.

Alteration of Sweet and Bitter Taste Sensitivity with Development of Glucose Intolerance in Non-insulin-Dependent Diabetes Mellitus Model OLETF Rats.

Patients with diabetes exhibit altered taste sensitivity, but its details have not been clarified yet. Here, we examined alteration of sweet taste sensitivity with development of glucose intolerance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of non-insulin-dependent diabetes mellitus. Compared to the cases of Long Evans Tokushima Otsuka (LETO) rats as a control, glucose tolerance of OLETF rats decreased with aging, resulting in development of diabetes at 36-weeks-old. In brief-access tests with a mixture of sucrose and quinine hydrochloride, OLETF rats at 25 or more-weeks-old seemed to exhibit lower sweet taste sensitivity than age-matched LETO ones, but the lick ratios of LETO, but not OLETF, rats for the mixture and quinine hydrochloride solutions decreased and increased, respectively, aging-dependently. Expression of sweet taste receptors, T1R2 and T1R3, in circumvallate papillae (CP) was almost the same in LETO and OLETF rats at 10- and 40-weeks-old, while expression levels of a bitter taste receptor, T2R16, were greater in 40-weeks-old rats than in 10-weeks-old ones in both strains. There was no apparent morphological alteration in taste buds in CP between 10- and 40-weeks-old LETO and OLETF rats. Metagenomic analysis of gut microbiota revealed strain- and aging-dependent alteration of mucus layer-regulatory microbiota. Collectively, we concluded that the apparent higher sweet taste sensitivity in 25 or more-weeks-old OLETF rats than in age-matched LETO rats was due to the aging-dependent increase of bitter taste sensitivity in LETO rats with alteration of the gut microbiota.

Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials.

BACKGROUND: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. METHODS: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). RESULTS: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. CONCLUSIONS: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. TRIAL REGISTRATION: Not applicable (pooled analysis).

Correlational analysis between salivary and blood glucose levels in individuals with and without diabetes mellitus: a cross-sectional study.

OBJECTIVE: To estimate the association of patient-related demographic, socioeconomic status, physical activity, stress, and dietary factors influencing the relationship between salivary and blood glucose levels in individuals with and without diabetes mellitus (DM). METHOD: This cross-sectional study was conducted on 166 participants with and without DM. Saliva and blood were collected to estimate the glucose levels. Age, gender, occupation, socioeconomic and education level, BMI, hip to waist circumference, stress, dietary pattern, lifestyle, physical activity, family history of diabetes, and type of diabetes were recorded. The association of saliva to predict blood glucose levels was analysed using Spearman Rank Correlation and how these patient-related factors influence the correlation was estimated for future machine learning models. The difference in medians for various groups was calculated using the Mann-Whitney U Test or Kruskal Wallis Test. RESULTS: Blood glucose level is not significantly correlated to salivary glucose level. However, a statistically significant difference in the median blood glucose levels for diabetic participants (median = 137) compared to healthy controls (p-value < .05) was noted. The correlation between blood and salivary glucose was more positive for higher levels of glucose (Spearman 0.4). Age, alcohol consumption, monthly wages, intake of vegetables, and socioeconomic status affect blood glucose levels. CONCLUSION: A correlation between saliva and blood glucose levels in healthy individuals was weak. Saliva should only be used as a monitoring tool rather than a diagnostic tool and is more reliable for patients with poorly controlled diabetes mellitus.

Effectiveness of Combined Aerobic and Resistance Exercise on Cognition, Metabolic Health, Physical Function, and Health-related Quality of Life in Middle-aged and Older Adults With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the effectiveness of combined aerobic and resistance exercise on cognition, metabolic health, physical function, and health-related quality of life (HRQoL) in middle-aged and older adults with type 2 diabetes mellitus (T2DM). DATA SOURCE AND STUDY SELECTION: Systematic search of CINAHL, Cochrane, EMBASE, Scopus, PubMed, ProQuest Dissertation and Thesis, PsycINFO, Web of Science databases, and gray literature from Google Scholar. Pertinent randomized controlled trials (RCTs) were selected. The Protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42023387336). DATA EXTRACTION: The risk of bias was evaluated using the Cochrane Risk of Bias tool by 2 reviewers independently. Outcome data were extracted in a fixed-effect model if heterogeneity test were not significant and I2≤50%; otherwise, the random-effects model was used. DATA SYNTHESIS: Sixteen studies with 2426 participants were included in this review. Combined aerobic and resistance exercise had significant positive effects on cognition (SMD=0.34, 95% CI: 0.13 to 0.55), metabolic health on HbA1c (SMD=-0.35, 95% CI: -0.48 to -0.22) and lipid profile (total cholesterol SMD=-0.20, 95% CI: -0.34 to -0.07; low-density lipoprotein SMD=-0.19, 95% CI: -0.33 to -0.05; high-density lipoprotein SMD=0.25, 95% CI: 0.12 to 0.39; and triglycerides SMD=-0.18, 95% CI: -0.31 to -0.04), physical function on aerobic oxygen uptake (SMD=0.58, 95% CI: 0.21 to 0.95) and body mass index (MD=-1.33, 95% CI: -1.84 to -0.82), and physical HRQoL (MD=4.17, 95% CI: 0.86 to 7.48). Our results showed that clinically important effects on cognition may occur in combining the low-moderate intensity of aerobic exercise and progressive intensity of resistance training, the total duration of the exercise needs to be at least 135 minutes per week, among which, resistance training should be at least 60 minutes. CONCLUSION: Combined aerobic and resistance exercise effectively improves cognition, ameliorates metabolic health, enhances physical function, and increases physical HRQoL in middle-aged and older adults with T2DM. More RCTs and longitudinal follow-ups are required to provide future evidence of structured combined aerobic and resistance exercise on other domains of cognition.

Clinical insights into the cross-link between mood disorders and type 2 diabetes: A review of longitudinal studies and Mendelian randomisation analyses.

Mood disorders and type 2 diabetes mellitus (T2DM) are prevalent conditions that often co-occur. We reviewed the available evidence from longitudinal and Mendelian randomisation (MR) studies on the relationship between major depressive disorder (MDD), bipolar disorder and T2DM. The clinical implications of this comorbidity on the course of either condition and the impact of antidepressants, mood stabilisers, and antidiabetic drugs were examined. Consistent evidence indicates a bidirectional association between mood disorders and T2DM. T2DM leads to more severe depression, whereas depression is associated with more complications and higher mortality in T2DM. MR studies demonstrated a causal effect of MDD on T2DM in Europeans, while a suggestive causal association in the opposite direction was found in East Asians. Antidepressants, but not lithium, were associated with a higher T2DM risk in the long-term, but confounders cannot be excluded. Some oral antidiabetics, such as pioglitazone and liraglutide, may be effective on depressive and cognitive symptoms. Studies in multi-ethnic populations, with a more careful assessment of confounders and appropriate power, would be important.

Vitamin K1 Intake and Incident Diabetes in the Danish Diet, Cancer, and Health Study.

CONTEXT: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors. OBJECTIVE: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes. METHODS: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models. RESULTS: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups. CONCLUSION: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity).

Severe hypoglycemia and risk of hospitalization for heart failure in adults with diabetes treated with oral medications with or without insulin: A population-based study.

AIMS: We aimed to determine if severe hypoglycemia (SH) independently increases the risk of hospitalization for heart failure (hHF) in type 2 diabetes, regardless of the prevalent or incident cardiovascular disease (CVD). METHODS: This was a nationwide population-based propensity score-matched study using Korean National Health Insurance Service data (2002-2018). The hazards of hHF were compared in individuals who experienced SH (n = 8,965) and 1:3 matched controls, among adults with diabetes using oral anti-diabetes medications (OADs) with or without insulin and without previous hHF at baseline. RESULTS: During 236,417 person-years, 1,189 cases of hHF occurred. The hazard of hHF was higher in individuals with SH compared to matched controls (adjusted hazard ratio [aHR] 1.503, 95 % confidence interval [CI] 1.324-1.707). The increase in aHR remained significant when excluding participants with prevalent or incident major adverse cardiovascular events (MACE; aHR 1.352, 95 % CI 1.228-1.622) and any CVD (aHR 1.342, 95 % CI 1.025-1.756). Two or more SH events were associated with further increase in hHF risk. CONCLUSION: SH was associated with increased risks of hHF among adults with diabetes using OAD with or without insulin. The increased risk was attenuated but remained significant in those without prevalent or incident MACE or CVDs.

In-vivo hyperglycemic, antioxidant, histopathological changes, and simultaneous measurement of kaempferol verified by high-performance thin layer chromatography of Setaria italica in streptozotocin -induced diabetic rats.

Background: Setaria italica (common name- foxtail, kangni) is one of the major food crops which is prominently cultivated in southern regions of India and in certain regions of Uttar Pradesh. Besides the crop's consumption as a general source of carbohydrate rich cereal, the seeds of the crop are comprised of more fiber. So, it is recommended to add in the dietary supplementation of the diabetic people across the country. Objective: In this paper, it intends to investigate the antidiabetic activity and antioxidant activity of S. italica (foxtail millet) seeds in diabetic rats. Methods: The six genotypes of foxtail millets (S. italica) namely Kangni-1, Kangni-4, Kangni-5, Kangni-6, Kangni-7 & Kangni-10 respectively were subjected to in vitro investigations via. comprehensive metabolic panel (CMP) involving blood glucose study, Kidney & Liver function test, and antioxidant study (Catalase test; Glutathione S-transferase (GST); Superoxide Dismutase (SOD); glutathione (GSH); hiobarbituric acid reactive substances (TBARS) & Glutathione peroxidase (GPx) and were performed in vivo animal investigations in Wistar rats. The STZ induced diabetic rats were fed with doses of different S. italica seed aqueous extract to evaluate its anti-hyperglycemic activity by oral administration of SISAE. Further, it was compared with Glibenclamide which acts as one of the standard oral hypoglycemic agents. Results: From achieved outcomes, a significant fall of blood glucose level (70%) produced 300 mg SISAE/kg b.w. after 6 h of extract administration. However, no change could be produced by these doses of the SISAE in normal rats' blood glucose levels. A significant fall in glucose level along with significant glycemic control by lower HbA1c levels was observed in diabetic treated rats after 3 weeks of treatment with 300 mg of SISAE/kg b.w./day when comparing to untreated diabetic rats. Among these five genotypes of S. italica, the differences in the glycemic index were found. a significant fall could be found in blood glucose levels of Wistar rats, when every experimental rat was incorporating with the extract of different genotypes of Setaria italica L. Beauv than the rats treated with Glibenclamide in every 7 days of interval. The level of catalase, SOD, GST, GPx, GSH and TBARS showed variation while the rats were fed with the extract of S. italica in the liver test of rats. In kidney function test, the result shows that there is significant relationship between foxtail extract and kidney function of STZ induced diabetes rats. They show the change in their serum creatinine level, serum urea and serum uric acid. Conclusion: The result obtained from the study shows that the extract of S. italica seeds is capable for the hypolipidemic and antihyperglycemic activities, thereby, they serve as one of the good sources for herbal medicinal items.

Use of Continuous Glucose Monitoring in the Assessment and Management of Patients With Diabetes and Chronic Kidney Disease.

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to 'burnt-out' beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.

Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.

OBJECTIVE: The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS: Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS: L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION: L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.

Management of Patients with Newly Diagnosed Diabetic Mellitus: Ophthalmologic Outcomes in Intensive versus Conventional Glycemic Control.

BACKGROUND AND OBJECTIVE: Diabetic retinopathy, a microvascular complication of diabetes mellitus, is one of the most important causes of visual loss in developed countries. Our objective is to evaluate the efficacy of intensive versus conventional glycemic control of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients in terms of ophthalmologic outcome, pathogenesis of the early worsening of diabetic retinopathy, risk factors for early worsening and diabetic retinopathy progression. METHODS: A literature search on publications concerning glycaemic control in diabetic retinopathy and management of newly diagnosed diabetes mellitus by intensive versus conventional glycaemic control. RESULTS: A total of 22 articles were reviewed after curation by the authors for relevance. Nineteen articles are randomized control trial, 2 articles are observational studies and 1 is clinical trial. Fifteen articles investigated the glycaemic control in T1DM-related diabetic retinopathy and 8 on T2DM-related diabetic retinopathy. The level of glycemia (in terms of HbA1c level) is significantly related to the diabetic retinopathy progression in both T1DM and T2DM. Intensive glycemic control was found to reduce the development of severe diabetic retinopathy, including severe non-proliferative diabetic retinopathy, neovascularization, clinically significant macular edema and loss of vision. Early worsening of diabetic retinopathy commonly occurs during the first year of intensive treatment, especially those initially present with proliferative or severe non-proliferative retinopathy. However, most patients with early worsening can recover and their long-term ophthalmologic outcomes are better when compared to conventional glycemic control. CONCLUSION: The current guideline on HbA1c level is considered sufficient for the minimization of diabetic retinopathy progression. More frequent monitoring for early worsening should be recommended for newly diagnosed diabetes cases already presenting with retinopathy.

The role of hyperbaric oxygen to platelet aggregation in noninsulin-dependent diabetes mellitus (NIDDM).

OBJECTIVES: Hyperglycemia in diabetes mellitus (DM) could cause rheological disorder, such as platelet aggregation and blood hyperviscosity. Hyperbaric oxygen (HBO) could decrease collagen as platelet aggregation agonist. This study aimed to explore the effect of HBO treatment to platelet aggregation parameters (latency time(LT), aggregation speed, aggregation index, and aggregation percentage) with the collagen aggregator in the noninsulin dependent diabetes mellitus (NIDDM). METHODS: The number of subjects in this study were 16 for each group normoxia normobaric (NONB) and HBO. NIDDM patients from DM polyclinic in Rumah Sakit Angkatan Laut (RSAL) Dr Ramelan Surabaya which was fulfilled inclusion criteria would receive HBO Therapy. Control Group/NONB were treated with NONB condition (20% O2 1 ATA) for 90 min and treatment group/HBO were treated with hyperoxia hyperbaric condition (100% O2 2.4 ATA) for 3 × 30 min with interval of 2 × 5 min for inhaling fresh air. Subject has been blood taken for platelet aggregation test before and after HBO Therapy. The length of treatment was 5 days for both condition (NONB and HBO). RESULTS: The data from both groups, NONB and HBO were tested first by normality test, homogenity test, correlation test, analysis of covariance, and paired t-test. Based on paired t-test, the decrease on platelet aggregation speed, aggregation index, and aggregation percentage after HBO treatment was showed significant difference on the LT and aggregation index while in aggregation speed and aggregation percentage was not significant. NONB group after 5 days was showed a significant difference on the aggregation speed and aggregation index while in LT and aggregation percentage was not significant. CONCLUSIONS: The utilization of HBO 2.4 ATA 100% O2 3 × 30 min, once a day, for 5 days could decrease the platelet aggregation parameters (LT, aggregation speed, aggregation index, and aggregation percentage) in patients with NIDDM.

The impact of long-term corticosteroid use on acute postoperative complications following lumbar decompression surgery.

BACKGROUND: Corticosteroids have a negative impact on the human immune system's ability to function at an optimal level. Studies have shown that patients on long-term corticosteroids have higher infection rates. However, the rates of infection and other complications following lumbar decompression surgery remains under-investigated. The aim of our study was to determine the impact of preoperative long-term corticosteroid usage on acute, 30-day postoperative complications in a subset of patients undergoing lumbar spine decompression surgery, without fusion or instrumentation. We hypothesize that patients on long-term corticosteroids will have higher rates of infection and other postoperative complications after undergoing lumbar decompression surgery of the spine. METHODS: A retrospective cohort study was conducted using data collected from the National Surgical Quality Improvement Program database data from 2005 to 2016. Lumbar decompression surgeries, including discectomies, laminectomies, and others were identified using CPT codes. Chi-square analysis was used to evaluate differences among the corticosteroid and non-corticosteroid groups for demographics, preoperative comorbidities, and postoperative complications. Logistic regression analysis was done to determine if long-term corticosteroid use predicts incidence of postoperative infections following adjustment. RESULTS: 26,734 subjects met inclusion criteria. A total of 1044 patients (3.9%) were on long-term corticosteroids prior to surgical intervention, and 25,690 patients (96.1%) were not on long-term corticosteroids. Patients on long-term corticosteroids were more likely to be older (p < 0.001), female (p < 0.001), nonsmokers (p < 0.001), and have a higher American Society of Anesthesiologist class (p < 0.001). Multivariate analysis demonstrated that long-term corticosteroid usage was associated with increased overall complications (odds ratio [OR]: 1.543; p < 0.001), and an independent risk factor for the development of minor complications (OR: 1.808; p < 0.001), urinary tract infection (OR: 2.033; p = 0.002), extended length of stay (OR: 1.244; p = 0.039), thromboembolic complications (OR: 1.919; p = 0.023), and sepsis complications (OR: 2.032; p = 0.024). CONCLUSION: Long-term corticosteroid usage is associated with a significant increased risk of acute postoperative complication development, including urinary tract infection, sepsis and septic shock, thromboembolic complications, and extended length of hospital stay, but not with superficial or deep infection in patients undergoing lumbar decompression procedures. Spine surgeons should remain vigilant regarding postoperative complications in patients on long-term corticosteroids, especially as it relates to UTI and propensity to decompensate into sepsis or septic shock. Thromboembolic risk attenuation is also imperative in this patient group during the postoperative period and the surgeon should weigh the risks and benefits of more intensive anticoagulation measures.

Paraoxonase 1 gene polymorphisms concerning non-insulin-dependent diabetes mellitus nephropathy in hemodialysis patients.

AIMS: Data on involvement of paraoxonase 1 gene (PON1) in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy are scarce. We investigated PON1 polymorphisms concerning end-stage NIDDM nephropathy and atherosclerotic complications in NIDDM nephropathy patients treated with hemodialysis (HD). METHODS: In NIDDM nephropathy (n = 402) and non-diabetic (n = 998) HD subjects, we obtained PON1 polymorphisms by HRM analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). RESULTS: Only PON1 rs705379 was associated with end-stage NIDDM nephropathy in the recessive (OR 1.451, 95% CI 1.104-1.906, P = 0.009) and additive (OR 1.398, 95%CI 1.009-1.936, P = 0.046) inheritance modes. NIDDM nephropathy patients bearing the rs854560 T allele were at higher risk for ischemic cerebral stroke (OR 2.087, 95%CI 1.145-3.801, P = 0.016). In non-diabetic patients but not NIDDM nephropathy subjects, atherogenic dyslipidemia corresponded with PON1 rs662 A allele and PON1 rs854560 TT homozygosity. CONCLUSIONS: In HD patients, NIDDM nephropathy correlates with the TT genotype of PON1 rs705379. The rs854560 T allele indicates a higher risk for atherosclerotic diseases in NIDDM nephropathy subjects. The T alleles of both PON1 SNVs are known as low expression variants downregulated serum PON1 activity. An increase of diminished PON1 activity may be a target in the prevention of NIDDM nephropathy and NIDDM atherosclerotic complications.

Impact of type 2 diabetes on postoperative outcome after hip fracture: nationwide population-based study in Taiwan.

The impact of diabetes mellitus (DM) on hip fracture (HFx) is still controversial. We used nationwide population-based data in Taiwan to observe postoperative outcomes of HFx in patients with type 2 diabetes mellitus (T2DM) and found that the impact of T2DM may be related to medication of blood glucose control. OBJECTIVE: Published studies evaluating diabetic patients with HFx have shown controversial outcomes. We assessed the impact of T2DM on postoperative outcomes after HFx in elderly patients using the nationwide population database in Taiwan. RESEARCH DESIGN AND METHODS: We used data from the National Health Research Institute in Taiwan to recruit patients who had undergone operations for HFx between 2000 and 2009. The recruited patients with T2DM were divided into the oral antidiabetic drug (OAD) cohort and the insulin cohort according to the use or non-use of insulin. Patients without DM were propensity score matched in a 1:1 ratio by four variables. We used the χ2 test, linear regression and Cox proportional hazards model to assess variables, including length of hospital stay, medical cost, complications, early readmission, and 1-year mortality. RESULTS: We identified 5490 subjects in total. The insulin cohort exhibited prolonged hospital stay (11.8 days), higher medical costs, more complications within 30 and 90 after hip surgery, earlier readmission, and higher 1 year mortality rate (25.8%) than the OAD and non-DM cohorts. The OAD cohort had longer hospital stay (10.1 days) and higher readmission rate but fewer complications and mortality rates (14.9%) than the non-DM cohort. CONCLUSIONS: After matching confounding factors, the T2DM with OAD control groups were not associated with higher complication or mortality rates but were associated with higher readmission rates. However, diabetic patients with insulin control have poor outcome. The impact of T2DM on the postoperative outcomes of patients with HFx may be related to blood glucose control medication.

Once-weekly semaglutide for patients with type 2 diabetes: a cost-effectiveness analysis in the Netherlands.

Objective: Choosing therapies for type 2 diabetes that are both effective and cost-effective is vital as healthcare systems worldwide aim to maximize health of the population. The present analysis assessed the cost-effectiveness of once-weekly semaglutide (a novel glucagon-like peptide-1 (GLP-1) receptor agonist) versus insulin glargine U100 (the most commonly used basal insulin) and versus dulaglutide (an alternative once-weekly GLP-1 receptor agonist), from a societal perspective in the Netherlands. Research design and methods: The IQVIA CORE Diabetes Model was used to project outcomes for once-weekly semaglutide 0.5 mg and 1 mg versus insulin glargine U100, once-weekly semaglutide 0.5 mg versus dulaglutide 0.75 mg, and once-weekly semaglutide 1 mg versus dulaglutide 1.5 mg. Clinical data were taken from the SUSTAIN 4 and SUSTAIN 7 clinical trials. The analysis captured direct and indirect costs, mortality, and the impact of diabetes-related complications on quality of life. Results: Projections of outcomes suggested that once-weekly semaglutide 0.5 mg was associated with improved quality-adjusted life expectancy by 0.19 quality-adjusted life years (QALYs) versus insulin glargine U100 and 0.07 QALYs versus dulaglutide 0.75 mg. Once-weekly semaglutide 1 mg was associated with mean increases in quality-adjusted life expectancy of 0.27 QALYs versus insulin glargine U100 and 0.13 QALYs versus dulaglutide 1.5 mg. Improvements came at an increased cost versus insulin glargine U100, with incremental cost-effectiveness ratios from a societal perspective of €4988 and €495 per QALY gained for once-weekly semaglutide 0.5 mg and 1 mg, respectively, falling below Netherlands-specific willingness-to-pay thresholds. Improvements versus dulaglutide came at a reduced cost from a societal perspective for both doses of once-weekly semaglutide. Conclusions: Once-weekly semaglutide is cost-effective versus insulin glargine U100, and dominant versus dulaglutide 0.75 and 1.5 mg for the treatment of type 2 diabetes, and represents a good use of healthcare resources in the Netherlands.

Graph-Based Predictive Modelling of Chronic Disease Development: Type 2 DM Case Study.

This study proposes a graph-based method for representing the dynamics of chronic diabetes as a complex process with different characteristics. The study was based on the case histories of 6864 patients with diabetes mellitus, 90% of whom suffer from type 2 diabetes. Our method allows to predict the sequence of events during the development of type 2 diabetes for each patient. Typical developmental trajectories of the disease were investigated, their clustering was carried out, the trajectory patterns were identified and studied. Based on the constructed directed graph reflecting transitions between different conditions of the patients, the clustering of diabetic statuses was carried out using the Modularity Class method; 8 clusters were selected, each of them was interpreted and studied. The method of the disease developmental trajectories creation by means of machine learning methods was described. Unlike static models of a disease course, this method considers complete past information on the patient and his or her previous events, using each event of the course of disease to predict the next event.