Browsing by Subject "GLYCEMIC CONTROL"

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  • Seidelmann, Sara B.; Feofanova, Elena; Yu, Bing; Franceschini, Nora; Claggett, Brian; Kuokkanen, Mikko; Puolijoki, Hannu; Ebeling, Tapani; Perola, Markus; Salomaa, Veikko; Shah, Amil; Coresh, Josef; Selvin, Elizabeth; MacRae, Calum A.; Cheng, Susan; Boerwinkle, Eric; Solomon, Scott D. (2018)
    BACKGROUND Loss-of-function mutations in the SGLT1 (sodium/glucose co-transporter-1) gene result in a rare glucose/galactose malabsorption disorder and neonatal death if untreated. In the general population, variants related to intestinal glucose absorption remain uncharacterized. OBJECTIVES The goat of this study was to identify functional SGLT1 gene variants and characterize their clinical consequences. METHODS Whole exome sequencing was performed in the ARIC (Atherosclerosis Risk in Communities) study participants enrolled from 4 U.S. communities. The association of functional, nonsynonymous substitutions in SGLT1 with 2-h oral glucose tolerance test results was determined. Variants related to impaired glucose tolerance were studied, and Mendelian randomization analysis of cardiometabotic outcomes was performed. RESULTS Among 5,687 European-American subjects (mean age 54 +/- 6 years; 47% mate), those who carried a haplotype of 3 missense mutations (frequency of 6.7%)-Asn51Ser, Ala411Thr, and His615Gln-had lower 2-h glucose and odds of impaired glucose tolerance than noncarriers (beta-coefficient: -8.0; 95% confidence interval [CI]: -12.7 to -3.3; OR: 0.71; 95% CI: 0.59 to 0.86, respectively). The association of the haplotype with oral glucose tolerance test results was consistent in a replication sample of 2,791 African-American subjects (beta = -16.3; 95% CI: -36.6 to 4.1; OR: 0.39; 95% CI: 0.17 to 0.91) and an external European-Finnish population sample of 6,784 subjects (beta = -3.2; 95% CI: -6.4 to 0.02; OR: 0.81; 95% CI: 0.68 to 0.98). Using a Mendelian randomization approach in the index cohort, the estimated 25-year effect of a reduction of 20 mg/dl in 2-h glucose via SGLT1 inhibition would be reduced prevalent obesity (OR: 0.43; 95% CI: 0.23 to 0.63), incident diabetes (hazard ratio [HR]: 0.58; 95% CI: 0.35 to 0.81), heart failure (HR: 0.53; 95% CI: 0.24 to 0.83), and death (HR: 0.66; 95% CI: 0.42 to 0.90). CONCLUSIONS Functionally damaging missense variants in SGLT1 protect from diet-induced hyperglycemia in multiple populations. Reduced intestinal glucose uptake may protect from long-term cardiometabolic outcomes, providing support for therapies that target SGLT1 function to prevent and treat metabolic conditions. (C) 2018 Published by Elsevier on behalf of the American College of Cardiology Foundation.
  • Koponen, Anne M.; Simonsen, Nina; Suominen, Sakari (2019)
    The results of this study showed the importance of autonomous motivation for healthy eating. Autonomous motivation and female gender were the determinants most strongly associated with fruits, vegetables, and berries intake among patients with type 2 diabetes. Other determinants of fruits, vegetables, and berries intake were high education, high social support, high age, and a strong sense of coherence. Autonomous motivation and self-care competence mediated the effect of perceived autonomy support from a physician on fruits, vegetables, and berries intake. Thus, physicians can promote patients' fruits, vegetables, and berries intake by supporting their autonomous motivation and self-care competence. The results are in line with self-determination theory.
  • Ibrahim, Mahmoud; Baker, Jason; Cahn, Avivit; Eckel, Robert H.; Sayed, Nuha Ali El; Fischl, Amy Hess; Gaede, Peter; Leslie, R. David; Pieralice, Silvia; Tuccinardi, Dario; Pozzilli, Paolo; Richelsen, Bjørn; Roitman, Eytan; Standl, Eberhard; Toledano, Yoel; Tuomilehto, Jaakko; Weber, Sandra L.; Umpierrez, Guillermo E. (2020)
    Abstract Hypoglycemia is common in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) and constitutes a major limiting factor in achieving glycemic control among people with diabetes. While hypoglycemia is defined as a blood glucose level under 70 mg/dL (3.9?mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycemic control. Severe hypoglycemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycemia is the most important safety outcome in clinical studies of glucose lowering agents. The ADA Standards of Medical Care recommends that a management protocol for hypoglycemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycemic events with the use of newer antidiabetic drugs. Increased hypoglycemia risk is observed with the use of insulin and/or sulfonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycemia and Cardiovascular (CV) outcomes show features of ?frailty?. Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. CGM should be considered for all individuals with increased risk for hypoglycemia, impaired hypoglycemia awareness, frequent nocturnal hypoglycemia and with history of severe hypoglycemia. Patients with impaired awareness of hypoglycemia (IAH) benefit from real-time continuous glucose monitoring (CGM). The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycemia. Several therapeutic considerations are important to reduce hypoglycemia risk during pregnancy including administration of rapid-acting insulin analogs rather than human insulin, pre-conception initiation of insulin analogs, and immediate postpartum insulin dose reduction. This article is protected by copyright. All rights reserved.
  • Lehtovuori, Tuomo; Kauppila, Timo; Kallio, Jouko; Heikkinen, Anna M.; Raina, Marko; Suominen, Lasse; Sund, Reijo (2018)
    Introduction. We studied whether primary care teams respond to financial group bonuses by improving the recording of diagnoses, whether this intervention leads to diagnoses reflecting the anticipated distribution of diseases, and how the recording of a significant chronic disease, diabetes, alters after the application of these bonuses. Methods. We performed an observational register-based retrospective quasi-experimental follow-up study with before-and-after setting and two control groups in primary healthcare of a Finnish town. We studied the rate of recorded diagnoses in visits to general practitioners with interrupted time series analysis. The distribution of these diagnoses was also recorded. Results. After group bonuses, the rate of recording diagnoses increased by 17.9% (95% CI: 13.6-22.3) but not in either of the controls (-2.0 to -0.3%). The increase in the rate of recorded diagnoses in the care teams varied between 14.9% (4.7-25.2) and 33.7% (26.6-41.3). The distribution of recorded diagnoses resembled the respective distribution of diagnoses in the former studies of diagnoses made in primary care. The rate of recorded diagnoses of diabetes did not increase just after the intervention. Conclusions. In primary care, the completeness of diagnosis recording can be, to varying degrees, influenced by group bonuses without guarantee that recording of clinically significant chronic diseases is improved.
  • Perkovic, Vlado; Agarwal, Rajiv; Fioretto, Paola; Hemmelgarn, Brenda R.; Levin, Adeera; Thomas, Merlin C.; Wanner, Christoph; Kasiske, Bertram L.; Wheeler, David C.; Groop, Per-Henrik; Conf Participants (2016)
    The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.
  • Haukka, Jani K.; Sandholm, Niina; Forsblom, Carol; Cobb, Jeffrey E.; Groop, Per-Henrik; Ferrannini, Ele (2018)
    Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98 sex-, age- and body mass index (BMI) matched nonprogressors remained normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening identified 1,242 metabolites, out of which 111 differed significantly between progressors and non-progressors after adjustment for age of diabetes onset, baseline glycosylated hemoglobin A1c (HbA(1c)), and albumin excretion rate (AER). The metabolites that predicted development of microalbumiuria included several uremic toxins and carnitine metabolism related molecules. Iterative variable selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5-aminovalerate as the best set of variables to predict development of microalbuminuria. A metabolomic index based on these metabolites improved the prediction of incident microalbuminuria on top of the clinical variables age of diabetes onset, baseline HbA1c and AER (ROCAUC = 0.842 vs 0.797), highlighting their ability to predict early-phase diabetic nephropathy.
  • Siljander, Heli; Honkanen, Jarno; Knip, Mikael (2019)
    The steep increase in the incidence of type 1 diabetes (T1D), in the Western world after World War II, cannot be explained solely by genetic factors but implies that this rise must be due to crucial interactions between predisposing genes and environmental changes. Three parallel phenomena in early childhood – the dynamic development of the immune system, maturation of the gut microbiome, and the appearance of the first T1D-associated autoantibodies – raise the question whether these phenomena might reflect causative relationships. Plenty of novel data on the role of the microbiome in the development of T1D has been published over recent years and this review summarizes recent findings regarding the associations between islet autoimmunity, T1D, and the intestinal microbiota.
  • Barlovic, Drazenka Pongrac; Tikkanen-Dolenc, Heidi; Groop, Per-Henrik (2019)
    Purpose of Review Physical activity is a fundamental part of lifestyle management in diabetes care. Although its benefits are very well recognized in the general population and in people with type 2 diabetes, much less is known about the effects of exercise in type 1 diabetes. In particular, exercise effects in relation to diabetic kidney disease (DKD) are understudied. Some uncertainties about physical activity recommendations stem from the fact that strenuous exercise may worsen albuminuria immediately after the activity. However, in middle-aged and older adults without diabetes, observational studies have suggested that physical activity is associated with a decreased risk of rapid kidney function deterioration. In this review, we focus on the role of physical activity in patients with DKD and type 1 diabetes.\ Recent Findings Hereby, we present data that show that in individuals at risk of DKD or with established DKD, regular moderate-to-vigorous physical activity was associated with reduced incidence and progression of DKD, as well as reduced risk of cardiovascular events and mortality. Summary Therefore, regular moderate-to-vigorous exercise should become a central part of the management of individuals with type 1 diabetes, in the absence of contraindications and accompanied with all needed educational support for optimal diabetes management.
  • Danni, Reeta; Viljanen, Antti; Aaronson, Alexander; Tuuminen, Raimo (2019)
    Purpose To examine preoperative anti-inflammatory treatment on recovery from cataract surgery in eyes of diabetic patients. Methods A Prospective randomized clinical trial. One hundred and three eyes of 103 patients with diabetes undergoing routine cataract surgery were randomized (1:1) not to receive any preoperative anti-inflammatory medication or to receive preoperative topical anti-inflammatory medication with a combination of prednisolone acetate (10 mg/ml) and nepafenac (1 mg/ml). All eyes received postoperative anti-inflammatory combination therapy for 3 weeks. Recovery from surgery was recorded by a structured home questionnaire. Clinical outcome parameters were recorded at 28 days and 3 months. Results Patient age and gender distribution, and all baseline ophthalmic and systemic parameters were comparable between the study groups. After surgery, conjunctival injection lasted 2.4 +/- 1.7 days (mean +/- SD) and irritation of the eye 3.3 +/- 3.9 days in eyes without preoperative treatment, when compared to 1.6 +/- 1.6 days (p = 0.067) and 2.4 +/- 4.0 days (p = 0.431), respectively, in eyes with preoperative treatment. At 28 days, central subfield macular thickness (CSMT) increased 2.2 +/- 20.2 mu m in eyes without preoperative treatment, when compared 0.1 +/- 25.2 mu m (p = 0.670) in eyes with preoperative treatment. At 3 months, the respective CSMT change from baseline was -1.5 +/- 26.9 mu m and -3.4 +/- 26.2 mu m (p = 0.762). None of the eyes were reported with pseudophakic cystoid macular oedema (PCME) in either group. Conclusion Lack of preoperative anti-inflammatory treatment does not impair recovery from surgery or predispose diabetic patients to increased risk of PCME in eyes postoperatively treated with combination therapy of prednisolone acetate and nepafenac.
  • Zonszein, Joel; Groop, Per-Henrik (2016)
    The duration of uncontrolled type 2 diabetes mellitus (T2DM) can adversely impact small and large vessels, eventually leading to microvascular and macrovascular complications. Failure of therapeutic lifestyle changes, monotherapy, and clinical inertia contribute to persistent hyperglycemia and disease progression. The aim was to review the complex pathophysiology of type 2 diabetes and how different oral agents can be used effectively as first-line therapy in combination with metformin, as well as in patients not achieving glycemic goals with metformin therapy. For this review, a non-systematic literature search of PubMed, NCBI, and Google Scholar was conducted. New oral agents have made it possible to improve glycemic control to near-normal levels with a low risk of hypoglycemia and without weight gain, and sometimes with weight loss. Early combination therapy is effective and has been shown to have a favorable legacy effect. A number of agents are available in a single-pill combination (SPC) that provides fewer pills and better adherence. Compared with adding a sulfonylurea, still the most common oral combination used, empagliflozin has been shown to decrease cardiovascular (CV) events in a dedicated CV outcome study, and pioglitazone has been effective in reducing the risk of secondary CV endpoints, whereas sulfonylureas have been associated with an increased risk of CV disease. In those failing metformin, triple oral therapy by adding a non-metformin SPC such as empagliflozin/linagliptin or pioglitazone/alogliptin is a good option for reducing glycated hemoglobin (HbA1c) without significant hypoglycemia. Clinicians have a comprehensive armamentarium of medications to treat patients with T2DM. Clinical evidence has shown that dual or triple oral combination therapy is effective for glycemic control, and early treatment is effective in getting patients to goal more quickly. Use of SPCs is an option for double or triple oral combination therapy and may result in better adherence.
  • Koponen, Anne M.; Simonsen, Nina; Suominen, Sakari (2018)
    Based on self-determination theory (SDT), this study investigated whether the three central SDT variablesperceived autonomy support (from a physician), autonomous motivation and self-care competencewere associated with success in weight management (SWM) among primary care patients with type 2 diabetes when the effect of other important life-context factors was controlled for. Patients participated in a mail survey in 2011. Those who had tried to change their health behavior during the past two years in order to lose weight, either with or without success (n = 1433, mean age 63years, 50% men), were included in this study. The successors were more autonomously motivated and energetic than the non-successors. Moreover, male gender, younger age, taking oral medication only, and receiving less social support in diabetes care predicted better success. Autonomous motivation predicted SWM; self-care competence also played a role by partly mediating the effect of autonomous motivation on SWM. These results support the idea of SDT that internalizing the value of weight management and its health benefits is necessary for long-term maintenance of health behavior change. Perceived autonomy support was not directly associated with SWM. However, physicians can promote patients' weight management by supporting their autonomous motivation and self-care competence.
  • Thomas, Merlin C.; Paldanius, Paivi M.; Ayyagari, Rajeev; Ong, Siew Hwa; Groop, Per-Henrik (2016)
    Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify aeyen12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in aeyen50 patients with T2DM and RI. Outcomes of interest included change in glycated hemoglobin (HbA1c), overall safety, and incidence of hypoglycemic events (HEs). Seven trials of aecurrency sign52-54 weeks duration were retrieved, which included one study each on vildagliptin, saxagliptin, and sitagliptin, two on linagliptin, and the remaining two were extension studies of vildagliptin and saxagliptin. Majority of patients were on insulin at baseline (53-86%), except in the sitagliptin study, where approximately 11% received insulin during the placebo-controlled phase. After 52 weeks, vildagliptin and saxagliptin reduced HbA1c levels by 0.6-0.7% (baseline 7.8-8.4%) versus placebo in the overall population. HbA1c reductions were similar at weeks 12 and 52. In the 12-week, placebo-controlled phase, sitagliptin and linagliptin reduced mean HbA1c by approximately 0.4% (baseline 7.7-8.1%) versus placebo. Rates of HEs with DPP-4 inhibitors were not significantly different versus placebo in any study. Rates of adverse events (AEs) and changes involving renal function were similar in the active- and placebo-treated groups. These results suggest that DPP-4 inhibitors have the potential to improve glycemic control in patients with RI without increasing the risk of HEs or overall AEs. Novartis Pharma AG.
  • Ahola, Aila J.; Harjutsalo, Valma; Thorn, Lena; Freese, Riitta; Forsblom, Carol; Mäkimattila, Sari; Groop, Per-Henrik; FinnDiane Study Grp (2017)
    Diet is a major modifiable lifestyle factor that may affect the components of the metabolic syndrome. We aimed to investigate the association between relative proportions of macronutrients and the components of the metabolic syndrome in a population of individuals with type 1 diabetes. In all, 791 individuals without nephropathy, with plausible energy intake and known metabolic syndrome status, taking part in the Finnish Diabetic Nephropathy Study were included in the analyses. Dietary data were collected with a diet record. The association between the relative macronutrient intake and the outcome variables were analysed using multivariable nutrient density substitution models. The relative proportions of dietary macronutrients or fatty acids were not associated with the presence of the metabolic syndrome. In men, however, favouring carbohydrates over fats was associated with lower odds of the waist component, whereas favouring either carbohydrates or fats over proteins was associated with lower odds of the blood pressure component of the metabolic syndrome. In women, substituting carbohydrates for fats was associated with lower HDL-cholesterol concentration. Substituting carbohydrates or fats for alcohol or protein was, in men, associated with lower systolic blood pressure. To conclude, the relative distribution of macronutrients may have some relevance for the metabolic syndrome.