Insulin as Monotherapy and in Combination with Other Glucose-Lowering Drugs Is Related to Increased Risk of Diagnosis of Pneumonia: A Longitudinal Assessment over Two Years

Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p < 0.001); insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p < 0.001); metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p < 0.001); statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001); as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.

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Nephrolithiasis against type 2 diabetes mellitus: on the effect of hypoglycemic therapy on lithogenesis

Terapevticheskii arkhiv ◽

10.26442/terarkh201890104-64 ◽

2018 ◽

Vol 90 (10) ◽

pp. 60-64

Author(s):

S K Yarovoy ◽

E N Kareva ◽

O V Djalilov

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Negative Impact ◽

Stone Formation ◽

Hypoglycemic Agents ◽

Control Group ◽

City Hospital ◽

Increased Risk

Aim. To study the effects of oral hypoglycemic agents that can affect the probability of recurrence of nephrolithiasis. Materials and methods. The article is based on the results of examination and treatment of 315 patients suffering from recurrent nephrolithiasis and medically compensated type 2 diabetes mellitus treated at the N.A. Lopatkin Institute of Urology and Interventional Radiology - the branch of the SMRC of Radiology, Ministry of Health of Russia and D.D. Pletnev City Hospital Moscow Healthcare Department in 2012-2017. The patients were divided into three groups according to the applied tool antidiabetic: metformin, glibenclamide, canagliflozin. The control group consisted of patients receiving insulin therapy. Results and discussion. The propensity of Metformin to reduce the pH of urine, which has a negative impact in the conditions of urate nephrolithiasis, which is most common in the population of patients with type 2 diabetes mellitus. Glibenclamide, on the contrary, somewhat latches urine. But changes in the reaction of urine under the influence of the drug do not go beyond normal values and are not clinically significant. Canagliflozin increases diuresis due to medication induced glycosuria and stimulates renal excretion of uric acid and its salts. However canagliflozin does not cause significant shifts in the pH of urine that may somewhat negates the increased risk of recurrence of urate stone formation in the background of the uricosuric effect of the drug. Conclusion. Drug therapy of type 2 diabetes mellitus significantly affects the properties of urine from patients with nephrolithiasis.

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PECAM-1 gene polymorphism (rs668) and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2016-0008 ◽

2016 ◽

Vol 19 (1) ◽

pp. 63-70 ◽

Cited By ~ 3

Author(s):

D Popović ◽

J Nikolajević Starčević ◽

M Šantl Letonja ◽

J Makuc ◽

A Cokan Vujkovac ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphism ◽

Carotid Atherosclerosis ◽

Control Group ◽

Minor Effect ◽

Initial Examination ◽

Increased Risk

ABSTRACTThe platelet endothelial cell adhesion molecule 1 (PECAM-1) plays an important role in many inflammatory processes, including the development of atherosclerosis. Polymorphism rs668 of the PECAM-1 gene (373C/G) is functional, and it was reported to be associated with increased serum levels of PECAM-1. We investigated the association between the rs668 polymorphism of PECAM-1 and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Geno-typing of the PECAM-1 gene polymorphism (rs668) was performed using KASPar assays. The control examinations were performed 3.8 ± 0.5 years after the initial examination. Higher CIMT was found in patients with T2DM in comparison with subjects without T2DM. Statistically sig-nificantly faster progression of the atherosclerotic markers was shown in subjects with T2DM in comparison with the control group. When adjusted to other risk factors, the rs668 GG genotype was associated with an increased risk of carotid plaques in subjects with T2DM. We concluded that our study demonstrated a minor effect of the rs668 PECAM-1 on markers of carotid atherosclerosis in subjects with T2DM.

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Metformin Treatment Is Associated with a Decreased Risk of Nonproliferative Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study

Journal of Diabetes Research ◽

10.1155/2020/9161039 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Yu-Pei Fan ◽

Chien-Tung Wu ◽

Jiun-Lu Lin ◽

Chao A. Hsiung ◽

Hsiao Yu Liu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Combination Therapy ◽

Research Database ◽

Metformin Treatment ◽

Nonproliferative Diabetic Retinopathy ◽

Increased Risk

Purpose. To assess the relationship between metformin use and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate the effect of metformin dosage on reducing the incidence of DR. Methods. The study population included patients with newly diagnosed T2DM, who were aged ≥20 years and prescribed with antidiabetic drug therapy lasting ≥90 days, as identified using the National Health Insurance Research Database between 2000 and 2012. We matched metformin users and nonusers by a propensity score. Cox proportional hazard regression analyses were used to compute and compare the risk of developing nonproliferative diabetic retinopathy (NPDR) in metformin users and nonusers. Results. Overall, 10,044 T2DM patients were enrolled. Metformin treatment was associated with a lower risk of NPDR (aHR 0.76, 95% CI 0.68–0.87) and sight-threatening diabetic retinopathy (STDR, aHR 0.29, 95% CI 0.19–0.45); however, the reduction in risk was borderline significant for STDR progression among NPDR patients (aHR 0.54, 95% CI 0.28–1.01). Combination therapy of metformin and DPP-4i exhibited a stronger but inverse relationship with NPDR development (aHR 0.32, 95% CI 0.25–0.41), especially at early (<3 months) stages of metformin prescription. These inverse relationships were also evident at different metformin doses and in adapted Diabetes Complications Severity Index scores (aDCSI). Moreover, combination therapy of metformin with sulfonylureas was associated with an increased risk of NPDR. Conclusion. Metformin treatment in patients with T2DM was associated with a reduced risk of NPDR, and a potential trend was found for a reduced STDR risk in patients who had previously been diagnosed with NPDR. Combining metformin with DPP-4i seemingly had a significantly beneficial effect against NPDR risk, particularly when aDCSI scores were low, and when metformin was prescribed early after T2DM diagnosis. These results may recommend metformin for early treatment of T2DM.

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Effect of Total Amount of Metformin HCl on the Characteristics of Metformin-Ca Alginate Microspheres

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v5i12018.13-19 ◽

2019 ◽

Vol 5 (1) ◽

pp. 13 ◽

Cited By ~ 1

Author(s):

Dewi Melani Hariyadi ◽

Noorma Rosita ◽

Tiara Jeni Rosadi

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Statistical Analysis ◽

Antidiabetic Drugs ◽

Metformin Hydrochloride ◽

Antidiabetic Drug ◽

Ca Alginate ◽

Metformin Hcl

Introduction: Metformin hydrochloride (metformin HCl) is an antidiabetic drug that is specifically used for type 2 diabetes mellitus (DM) and belongs to the biguanide antidiabetic drugs. Objective: The aim of this research was to determine the effect of total amount of metformin HCl on the characteristics of metformin HCl-Ca alginate microspheres using aerosolization technique. Methods: The total amount of metformin were 0.5 g (F1); 1 g (F2); 1.5 g (F3) and 2 g (F4). Drug was encapsulated into alginate and was crosslinked using CaCl2. Results: The results showed that drug loadings were 5.09%; 9.61%; 13.11%; and 15.09% respectively, while the entrapment efficiencies were 48.35%; 41.99%; 38.67%; and 30.53%. The yields were 80.92%; 74.12%; 68.27%; and 59.11% respectively. Based on the statistical analysis, it was found that there were significant differences between formulas. Particles of formulas decreased as the amount of drug increased. The resulting sizes were 1.82 μm (F1); 1.96 μm (F2); 2.1 μm (F3); and 2.97 μm (F4). Conclusion: It can be concluded that amount of drug significantly affected the characteristics of metformin-alginate microspheres.

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The Risk Factors of Severe Hypoglycemia in Older Patients with Dementia and Type 2 Diabetes Mellitus

Journal of Personalized Medicine ◽

10.3390/jpm12010067 ◽

2022 ◽

Vol 12 (1) ◽

pp. 67

Author(s):

Nai-Ching Chen ◽

Chien-Liang Chen ◽

Feng-Chih Shen

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Older Patients ◽

Control Group ◽

Research Database ◽

Increased Risk

Background: The adequate glycemic control and risk factors for hypoglycemia in older patients with dementia and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to analyze the status of glycemic control and determine the risk of hypoglycemia among these groups. Methods: A hospital admission record due to hypoglycemia through an emergency room with glucose supplementation in the Chang Gung Memorial Hospital was identified as a hypoglycemic event. Patients with dementia and T2DM without hypoglycemic events throughout the study period were defined as the control group. We gathered patients aged ≥65 years with a diagnosis of Alzheimer’s dementia (AD) and T2DM between 2001 and 2018 in the Chang Gung Research Database (CGRD). We extracted data included medication use, diagnoses, and biochemistry data from hospital records. Results: A total of 3877 older patients with dementia and T2DM with regular visits to the outpatient department were enrolled in this study. During the two-year follow-up period, 494 participants (12.7%) experienced hypoglycemia. Multivariable logistic multivariable regression models for hypoglycemic events showed that metformin had a protective effect (odds ratio (OR) = 0.75, p = 0.023), insulin had the highest risk (OR = 4.64, p < 0.001). Hemoglobin A1c (HbA1c) levels were not correlated with hypoglycemic events (OR = 0.95, p = 0.140). Patients with hypoglycemic episodes had a significantly higher proportion of ≥2 Charlson Comorbidity Index scores than those without hypoglycemic episodes (83.2% versus 56.4%, p < 0.001). Conclusions: Drug regimen affects hypoglycemic episodes but not HbA1c in older patients with dementia and T2DM. In addition, patients with more comorbidities experience an increased risk of hypoglycemia.

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PARAMETERS OF BONE METABOLISM IN PRE-AND POSTMENOPAUSAL WOMEN WITH TYPE 2 DIABETES MELLITUS IN THE RATIONALE FOR THE CHOICE OF ANTIOSTEOPOROTIC THERAPY

Osteoporosis and Bone Diseases ◽

10.14341/osteo201338-12 ◽

2013 ◽

Vol 16 (3) ◽

pp. 8-12

Author(s):

L A Ruyatkina ◽

A V Lomova ◽

D S Ruyatkin ◽

V V Romanov

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Bone Remodeling ◽

Negative Relationship ◽

Control Group ◽

Tartrate Resistant Acid Phosphatase ◽

C Peptide ◽

Increased Risk

Introduction. Bone health in type 2 diabetes mellitus (T2DM) is discussed for a long time as a known fact for increased risk of fractures. Purpose. To estimate the parameters of bone remodeling in pre-andpostmenopausal women with T2DM. Materials and Methods. In a cross-sectional pilot study which included 80 women: 40 with T2DM and 40 without disturbances of glucose metabolism (K), divided into subgroups of premenopausal (pre) and natural menopause (post) — 20 patients each. Results and conclusions. We found a tendency toward a decrease in bone turnover in patients T2DM, a significant negative relationship with C-peptide and ALP in T2DM, a positive correlation with tartrate — resistant acid phosphatase in the control group, although the levels of C-peptide did not differ in patients with T2DM and in the control group . Identified characteristics of decreased bone remodeling in patients with T2DM pathogenically justify the use of anabolic antiosteoporotic drugs for treatment of osteoporosis in such patients.

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Obesity, Hyperinsulinemia, IGF-1, and Hyperglycemia as Risk Factors for Colorectal Cancer in Patients with Type 2 Diabetes mellitus

Family Medicine ◽

10.30841/2307-5112.1-2.2020.204412 ◽

2020 ◽

Vol 0 (1-2) ◽

pp. 60-63

Author(s):

Т. С. Вацеба

Keyword(s):

Diabetes Mellitus ◽

Colorectal Cancer ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Study Groups ◽

The Body ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Increased Risk

The latest studies prove an increased risk of colorectal cancer in patients with type 2 diabetes mellitus. The pathogenetic factors of type 2 diabetes have been recognized as mechanisms of association between these diseases. The objective: to investigate the effects of obesity, hyperinsulinemia, IGF-1 and hyperglycemia on the development of colorectal cancer in patients with type 2 diabetes. Materials and methods. 36 patients were divided into groups: I – healthy (control group), II – patients with type 2 diabetes mellitus, III – patients with colorectal cancer without diabetes, IV – patients with a combination of two diseases. Using the method of enzyme-linked immunosorbent assay were determined levels of insulin and insulin-like growth factor-1 (IGF-1). DM compensation was assessed by the level of glycosylated hemoglobin (HbA1c) that was determined by immuno-exchange chromatography. The data obtained were analyzed using Statistica 12.0 (StatSoft Inc.,USA). Differences between the values in the control and experimental groups were determined by the Student’s t-test. The differences were considered significant at р<0.05. Results. According to the data obtained, colorectal cancer was diagnosed in patients with the age of over 60 years old with obesity. The body mass index (BMI) in patients of all study groups was higher than 30 kg/m2. Patients of group IV with a combination of type 2 diabetes and a circle of rectal cancer had significantly higher BMI compared to the control group (р<0.05). Significant hyperinsulinemia and increased IGF-1 levels were detected in patients in all study groups (р<0.05). Most patients with diabetes in both groups had HbA1c levels higher than 7.5%. Conclusions. Obesity, hyperinsulinemia, increased bioavailability of IGF-1, and hyperglycemia are pathogenetic factors in the risk of colorectal cancer in patients with type 2 diabetes. Patients over the age of 55 with diabetes, obesity, and hyperinsulinemia are advised to be screened for colorectal cancer.

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The association between adiponectin G276T gene polymorphic marker and abdominal obesity in a Kyrgyz population

Problems of Endocrinology ◽

10.14341/probl201561146-50 ◽

2015 ◽

Vol 61 (1) ◽

pp. 46-50

Author(s):

Zh T Isakova ◽

E T Talaibekova ◽

O S Lunegova ◽

D A Asambarva ◽

A S Kerimkulova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Blood Glucose ◽

Abdominal Obesity ◽

Polymorphic Locus ◽

Control Group ◽

Increased Risk ◽

The Relationship

A population of ethnic Kyrgyz was examined with a view to elucidating the relationship between the adiponectin G276T gene polymorphic locus and the development of abdominal obesity (AO). The study included 288 subjects at the age between 40 and 70 years. 139 of them (81 women and 58 men) presented with AO while 149 without obesity (62 women and 87 men) constituted the control group. The measured anthropometric parameters included arterial pressure, blood glucose, insulin, and leptin levels, blood lipid composition. Genotypes of adiponectin (AN) G276T gene polymorphism were identified by means of PCR-RFLP analysis. The relationship between the presence of the adiponectin G276T gene polymorphic and the development of abdominal obesity in the women was demonstrated. Specifically, 31% of the women with AO were carriers of T allele compared with 17% in the control group (χ2=7.89; p =0.005). The GT + TT genotype and carriage of T allele were associated with an increased risk of development of abdominal obesity (OR=2.5; 95% CI = 1.25-4.97 for the genotype and OR = 2.2; 95% CI = 1.26-4.000 for the allele). No such relationship was documented among men. The women with AO and GT+TT genotype more frequently than homozygotes presented with type 2 diabetes mellitus (64 and 37% respectively; p=0.017), hypertriglyceridemia (41 and 16.2% respectively; p=0.016), and enhanced blood glucose level (7.74±3.3 and 6.52±1.17; p=0.033). Moreover, their HOMA index was higher than in the homozygotes (3.5±1.7 and 2.63±1.24 respectively; p=0.02). It is concluded that the adiponectin G276T gene polymorphic variant in the women of Kyrgyz ethnicity is associated with abdominal obesity, type 2 diabetes mellitus, hyperglycemia, and hypertriglyceridemia.

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Pathogenetic significance of single nucleotide polymorphisms in the gastric inhibitory polypeptide receptor gene for the development of carbohydrate metabolism disorders in obesity

Diabetes Mellitus ◽

10.14341/dm7927 ◽

2016 ◽

Vol 19 (6) ◽

pp. 457-463 ◽

Cited By ~ 2

Author(s):

Daria S. Skuratovskaia ◽

Maria A. Vasilenko ◽

Nikolai S. Fattakhov ◽

Elena V. Kirienkova ◽

Natalia I. Mironyuk ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Carbohydrate Metabolism ◽

Abdominal Obesity ◽

Serum Insulin ◽

Control Group ◽

C Peptide ◽

Increased Risk

Aim. To investigate the association of the GIPR gene polymorphisms rs2302382 and rs8111428 with increased risk of type 2 diabetes mellitus and abdominal obesity.Materials and methods. The study involved 163 patients with abdominal obesity (BMI, 39.5 ± 8.3 kg/m2; age, 44.7 ± 8.9 years; men, 61; women, 102), 72 with type 2 diabetes mellitus (BMI, 43.70 ± 9.32 kg/m2; age, 46.5 ± 10.1 years; men, 29; women, 43) and 91 patients without carbohydrate metabolism disorders (BMI, 36.13 ± 6.72 kg/m2; age, 43.93 ± 8.35 years; men, 32; women 59). The control group comprised 109 relatively healthy volunteers (BMI, 22.6 ± 2.7 kg/m2; age, 39.5 ± 7.6 years; men, 66; women, 43). Genotypes were analysed by real-time PCR and serum insulin and C-peptide levels were evaluated by ELISA.Results. The AA genotype in the rs2302382 polymorphism of GIPR was associated with an increased risk for type 2 diabetes mellitus in abdominal obesity and the CA genotype was associated with a reduced risk. In individuals with abdominal obesity and type 2 diabetes mellitus carrying the CA genotype in rs2302382 polymorphism of GIPR, serum insulin and C-peptide levels were elevated to 56.27 mU/L (55.49–58.41 mU/L) and 2.04 ng/ml (1.37–2.85 ng/ml), respectively (p 0.05). In obese patients with the same genotype and without type 2 diabetes, serum insulin levels and C-peptide levels were 22.73 mU/L (19.07–25.76 mU/L) and 0.73 ng/ml (0.53–1.03 ng/ml), respectively (p 0.05). The GIPR rs8111428 polymorphism was not associated with increased risk of type 2 diabetes mellitus in obesity for any of the groups examined.Conclusion. Serum insulin and C-peptide levels were increased in patients with abdominal obesity who were carriers of the CA genotype in the rs2302382 polymorphism of GIPR, which is associated with a decreased risk of type 2 diabetes mellitus in obesity compared with the CC genotype.

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