Intensified Insulin Treatment Research Articles

Current barriers to initiating insulin therapy in individuals with type 2 diabetes.

Insulin is an essential drug in the treatment of diabetes, often necessary for managing hyperglycemia in type 2 diabetes mellitus (T2DM). It should be considered in cases of severe hyperglycemia requiring hospitalization, after the failure of other treatments, in advanced chronic kidney disease, liver cirrhosis, post-transplant diabetes, or during pregnancy. Moreover, in specific patient subgroups, early initiation of insulin is crucial for hyperglycemia control and prevention of chronic complications. Clinical guidelines recommend initiating insulin when other treatments fail, although there are barriers that may delay its initiation. The timing of initiation depends on individual patient characteristics. Typically, insulinization starts by adding basal insulin to the patient's existing treatment and, if necessary, progresses by gradually introducing prandial insulin. Several barriers have been identified that hinder the initiation of insulin, including fear of hypoglycemia, lack of adherence, the need for glucose monitoring, the injection method of insulin administration, social rejection associated with the stigma of injections, weight gain, a sense of therapeutic failure at initiation, lack of experience among some healthcare professionals, and the delayed and reactive positioning of insulin in recent clinical guidelines. These barriers contribute, among other factors, to therapeutic inertia in initiating and intensifying insulin treatment and to patients' non-adherence. In this context, the development of once-weekly insulin formulations could improve initial acceptance, adherence, treatment satisfaction, and consequently, the quality of life for patients. Currently, two once-weekly basal insulins, insulin icodec and basal insulin BIF, which are in different stages of clinical development, may help. Their longer half-life translates to lower variability and reduced risk of hypoglycemia. This review addresses the need for insulin in T2DM, its positioning in clinical guidelines under specific circumstances, the current barriers to initiating and intensifying insulin treatment, and the potential role of once-weekly insulin formulations as a potential solution to facilitate timely initiation of insulinization, which would reduce therapeutic inertia and achieve better early control in people with T2DM.

Effect of a lifestyle intervention to prevent weight gain at initiation of insulin pump therapy in type 2 diabetes: A randomized, controlled, multicentre trial

Insulin pump therapy improves glycaemic control in individuals with type 2 diabetes. However, it may be associated with weight gain. Aim: To test the effectiveness of a six-month dietary and physical activity intervention, compared to usual care, on weight gain prevention after initiation of insulin pump. Methods: Multicentre randomized, controlled trial of 54 individuals. Primary endpoint was between group difference in weight gain at six-months. Results: Weight gain after 6 months of insulin pump treatment did not differ between groups: mean 3.2 (3.9) kg in the control group and 3.9 (3.8) kg in the intervention group, (p = 0.56). HbA1c improved without difference between groups. Post-hoc multivariate analysis of all participants found that weight gain was independently associated with younger age, active smoking, and the magnitude of HbA1c reduction. A 1 % decrease in HbA1c was associated with an increase of 0.94 kg [95 % Confidence Interval 0.47; 1.41], p < 0.001. Conclusions: Treatment intensification by insulin pump therapy in patients with type 2 diabetes is effective to improve glycaemic control. A gain of about 1 kg per 1 % drop in HbA1c can be expected after insulin treatment intensification. This weight gain was not prevented by a home-base, individualized, 6-months lifestyle intervention program.

Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background/Introduction Patients with type 1 diabetes mellitus (T1DM) present signs of vascular and endothelial dysfunction earlier compared to healthy individuals. According to clinical studies, SGLT-2i favorably affect cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the data regarding the efficacy of SGLT-2i on cardiovascular markers in patients with T1DM are scarce. Purpose We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 30 patients with T1DM and pour glycemic control who were under medication with insulin and received dapagliflozin (n=15) or intensification of insulin treatment (n=15) (control group). We measured at baseline and at four months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&amp;gt;0.05). After four months treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−41%, p&amp;lt;0.05), in PWV (−10%, p&amp;lt;0.05), in cSBP (−6%, p&amp;lt;0.05) and in GLS (+5%, P&amp;lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +3%, PWV: +2%, cSBP: −2%, GLS: −3% at 4 months, P&amp;gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after four months treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&amp;lt;0.05). Conclusions Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control. Funding Acknowledgement Type of funding sources: None.

Insulin edema in an adolescent girl with newly diagnosed Type 1 diabetes mellitus

Background: Insulin edema is a rare complication that can occur following either initiation or intensification of insulin treatment in Type 1 diabetes mellitus (DM). It is an under reported condition. Awareness of this complication among physicians is important for early identification of this condition, and prompt initiation of treatment. Clinical Description: We present an 11-year-old girl with 2-month history of weight loss and 1-month history of polyuria and polydipsia who presented to us in moderate diabetic ketoacidosis. She developed anasarca and pulmonary edema 3 days after starting insulin. She also developed transaminitis a serum serum glutamic-oxaloacetic transaminase of 81 U/L and serum glutamic pyruvic transaminase of 83 U/L. A diagnosis of insulin edema was established after ruling out other causes like severe anemia, renal, cardiac and allergic causes. We also present a brief review of seven similar cases that we identified on a literature search. Management and Outcome: This included salt and fluid restriction along with diuretics. Edema resoled after 4 days of treatment, while transaminitis took 7 days to normalize. Conclusion: This case report highlights the importance of early recognition of the rare complication of insulin edema which can avoid unnecessary anxiety on the part of both treating physicians and parents of patients with Type 1 DM.

Insulin Edema in Type 2 Diabetes Mellitus: A Case Report Study

Edema is a rare complication induced by insulin therapy, which is mostly developed after initiation or intensification of insulin treatment in diabetic patients. Edema can either be localized or generalized. Our patient was a 34-year-old woman with type 2 diabetes. She was under treatment with oral agents medication, but recently insulin therapy was initiated for her due to inability to control her hyperglycemia and development of diabetic ketoacidosis. The patient referred while suffering from bilateral lower extremity edema. During follow-up, her edema resolved spontaneously without any specific treatments. In this patient, the diagnosis of edema was based on ruling out other causes, along with more accurate blood glucose control during diabetic ketoacidosis process and spontaneous recovery. Based on our finding, it can be concluded that insulininduced edema is not a worrisome problem and in most cases, its symptoms resolve without treatment and through restricting the consumption of water and salt.

Type 1 Diabetes Mellitus Patient Presented with Insulin Edema only after Intensive Lifestyle Changes: A Case Report and Brief Review of the Literature

Insulin edema is considered a rare type of generalized edema that occurs after initiation or intensification of insulin treatment in patients with diabetes mellitus (DM). In this case report, we present a clinically significant edema that developed following a dramatic improvement in glycemic control after intensive improvement in lifestyle in a 13-year-old girl, with type 1 DM confirmed by positive anti-glutamic acid decarboxylase (anti-GAD) antibodies. She had poor glycemic control during 2 years of insulin therapy, and following lifestyle improvements (with no changes to her medications types or doses), she developed generalized body edema, and facial puffiness that resolved spontaneously, without any intervention.

Procoagulant activity in children and adolescents on intensive insulin therapy.

Type 1 diabetes is associated with atherothrombosis, but limited data exist on procoagulant activity in the young. We investigated procoagulant activity in children/adolescents with type 1 diabetes using intensified insulin treatment compared with controls in a 5-year follow-up study, and further any associations with cardiovascular risk factors. The study included 314 diabetes children/adolescents and 120 healthy controls. Prothrombin fragment 1+2 (F1+2), D-dimer, tissue-factor-procoagulant-activity (TF-PCA), and tissue-factor-pathway-inhibitor (TFPI) were analyzed with ELISAs. F1+2, D-dimer, and TF-PCA did not differ between the groups or correlate to HbA1c in the diabetes group at either time points. TFPI was significantly higher in the diabetes group compared with controls both at inclusion and follow-up (both P < .001). In the diabetes group, TFPI correlated significantly to HbA1c at both time points (r = 0.221 and 0.304, both P < .001). At follow-up, females using oral contraceptives had significantly elevated F1+2, D-dimer, and TF-PCA and lower TFPI compared to no-users (all P < .005), and females had lower TFPI (P = .017) and higher F1+2 compared with males (P = .052), also after adjusting for the use of oral contraceptives. The current results show similar procoagulant activity in children/adolescents with type 1 diabetes compared with controls over a 5-year period, indicating that these children using modern intensified insulin treatment are not at high thrombotic risk at younger age. The elevated levels of TFPI in the diabetes group, related to hyperglycaemia, are probably reflecting increased endothelial activation. These findings highlight the significance of optimal blood glucose control in children/adolescents with type 1 diabetes, to maintain a healthy endothelium.

Hemichorea after hypoglycemic episodes with negative MRI findings in an elderly woman with poorly controlled type 2 diabetes mellitus: a case report

BackgroundDiabetic chorea appears during the course of poorly-controlled diabetes. While chorea associated with diabetes mellitus usually occurs during hyperglycemic episodes, hypoglycemia can also cause diabetic chorea. Brain magnetic resonance imaging (MRI) is useful for evaluating the pathogenesis of diabetic chorea. However, several diabetic chorea cases have reportedly not shown abnormal high-intensity in the putamen and striatum on T1-weighted images.Case presentationWe report a 74-year-old woman who was admitted to our hospital for treatment of poorly-controlled type 2 diabetes mellitus. Intensified insulin treatment gradually normalizeed blood glucose, but on the 19th hospital day, after a blood glucose measurement of 49 mg/dL, she showed hemichorea of the left face, shoulder, arm and leg. MRI revealed no abnormalities of either the putamen or the striatum on T1-weighted images. She was treated with dopamine receptor antagonists, which alleviated her hemichorea symptoms and allowed discharge from the hospital. 1 year after the first hospitalization, she had to be readmitted because her glycemic control had markedly deteriorated. Glycemic control improved rapidly, and, because hemichorea did not recur, the dopamine receptor antagonists were stopped. 1 month later, however, hemichorea recurred. She resumed taking the dopamine receptor antagonists, resulting in immediate disappearance of the hemichorea.ConclusionsWe herein describe a rare case of diabetes-associated hemichorea occurring after hypoglycemic episodes without abnormal high-intensity findings in the basal ganglia on T1-weighted images. The hemichorea relapsed with cessation of dopamine receptor antagonists. This case also underscores the importance of longitudinal assessment and treatment for hemichorea after hypoglycemic episodes, even in the absence of MRI findings, in elderly diabetic patients.

Disturbed eating, illness perceptions, and coping among adults with type 1 diabetes on intensified insulin treatment, and their associations with metabolic control.

This study investigated associations between psychological aspects and metabolic control among adults with type 1 diabetes (n = 282). Linear regression analyses demonstrated that the illness perception personal control and the coping strategy seeking emotional social support explained 23.2 percent of the variance in hemoglobin A1c among females (β = 0.40, p < 0.001 and β = -0.22, p < 0.01, respectively). Among males, only personal control remained significant, explaining 13.9 percent of the variance in hemoglobin A1c (β = 0.37, p < 0.001). The associations between psychological correlates and hemoglobin A1c indicate that addressing such aspects clinically may facilitate metabolic control, thereby potentially contributing to reduce the risk of complications.

Long-Term Effects of Initiating Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring (CGM) in People with Type 1 Diabetes and Unsatisfactory Diabetes Control.

Background: We aimed to assess the long-term effects of the introduction of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D). Methods: A prospective single-centre cohort study including participants with T1D and HbA1c > 7.5%. After completing a course in flexible intensified insulin treatment (FIT), participants were offered treatment change to CSII/CGM. FIT participants with HbA1c ≤ 7.5% who remained on multiple daily injections (MDI) and without CGM were monitored as a separate cohort to compare the cumulative incidence of diabetic complications. Results: The study cohort included 41 participants with T1D (21 male/20 female). The mean age (±SD) at inclusion was 24.2 ± 10.9 years, the mean follow-up was 8.9 ± 2.8 years, and the mean diabetes duration at the end of the study was 15.9 ± 10.1 years. The mean HbA1c level before the introduction of CSII was 8.8 ± 1.3% (73 ± 8 mmol/mol), and decreased significantly thereafter to 8.0 ± 1.1% (63 ± 7 mmol/mol) (p = 0.0001), and further to 7.6 ± 1.1% (59 ± 11 mmol/mol) after the initiation of CGM (p = 0.051). In the MDI group the HbA1c levels did not change significantly during a mean follow-up of 6.8 ± 3.2 years. The frequency of severe hypoglycaemia after the introduction of CSII/CGM declined significantly (from 9.7 to 2.2 per 100 patient-years, p = 0.03), and the cumulative incidence of newly diagnosed diabetic microvascular complications were comparable between the study group and the observational cohort. Conclusion: In people with T1D and unsatisfactory diabetes control the introduction of CSII and CGM results in a substantial and long-term improvement.

Risk of severe hypoglycemia in T1DM over 30 years of follow-up in the DCCT/EDIC study

Professor Tamberlane and co-workers investigated the rates of severe hypoglycemia in the DCCT/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort after approximately 30 years of follow-up. In earlier studies, high rates of hypoglycemic episodes had been found to be associated with lower HbA1c levels and intensified insulin treatment strategies. Now, in this reanalysis and extensive follow-up of a sub-cohort of the initial DCCT cohort, it has become clear that rates of severe hypoglycemia equilibrated over time between the two DCCT/EDIC treatment groups, hence conventional and intensified treatment arms in association with advancing duration of diabetes and similar HbA1c levels.

Effect of inositol stereoisomers at different dosages in gestational diabetes: an open-label, parallel, randomized controlled trial.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women. Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000mg myo-inositol plus 400mcg folic acid (MI treatment), 500mg D-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27.6mg myo/D-chiro-inositol plus 400 mcg folic acid (MI plus DCI treatment). The homeostasis model assessment of insulin resistance (HOMA-IR) was measured at the diagnosis of GDM and after 8weeks of treatment. Secondary outcomes, obstetric outcomes and any maternal or fetal complication at delivery were also collected. Eighty GDM women were assigned to one of the four arms of study (20 per arm). A significant delta decrease in HOMA-IR index was found in subjects of MI group without insulin therapy compared to control group (p < 0.001). A lower variation in average weight gain (at delivery vs pre-pregnancy and OGTT period) was detected in MI group vs control group (p = 0.001 and p = 0.019, respectively). Moreover, women exposed to MI and MI plus DCI required a significantly lower necessity of an intensified insulin treatment. Women of the control group had newborns with higher birth weight compared with women treated with inositol (p = 0.032). Our study provides interesting but preliminary results about the potential role of inositol stereoisomers supplementation in the treatment of GDM on insulin resistance levels and several maternal-fetal outcomes. Further studies are required to examine the optimal and effective dosages of different inositol supplements. CLINICAL TRIAL REG. NO.: NCT02097069, ClinicalTrial.gov.

Impact of an integrated care program on glycemic control and cardiovascular risk factors in patients with type 2 diabetes in Saudi Arabia: an interventional parallel-group controlled study

BackgroundLong intervals between patient visits and limited time with patients can result in clinical inertia and suboptimal achievement of treatment goals. These obstacles can be improved with a multidisciplinary care program. The present study aimed to assess the impact of such a program on glycemic control and cardiovascular risk factors.MethodsIn a randomized, parallel-group trial, we assigned 263 patients with poorly controlled type 2 diabetes mellitus (T2DM) to either a control group, standard care program, or a multidisciplinary care program involving a senior family physician, clinical pharmacy specialist, dietician, diabetic educator, health educator, and social worker. The participants were followed for a median of 10 months, between September 2013 and September 2014. Glycated hemoglobin (HbA1c), fasting blood glucose (FBG), lipid profiles, and blood pressure (BP) were measured. The assignment was blinded for the assessors of the study outcomes. The study registry number is.ResultsIn the intervention group, there were statistically significant (p < 0.05) post-intervention (relative) reductions in the levels of HbA1c (−27.1%, 95% CI = −28.9%, −25.3%), FBG (−17.10%, 95% CI = −23.3%, −10.9%), total cholesterol (−9.93%, 95% CI = −12.7%, −7.9%), LDL cholesterol (−11.4%, 95% CI = −19.4%, −3.5%), systolic BP (−1.5%, 95% CI = −2.9%, −0.03%), and diastolic BP (−3.4%, 95% CI = −5.2%, −1.7%). There was a significant decrease in the number of patients with a HbA1c ≥10 (86 mmol/mol) from 167 patients at enrollment to 11 patients after intervention (p < 0.001). However, the intervention group experienced a statistically significant increase in body weight (3.7%, 95% CI = 2.9%, 4.5%). In the control group, no statistically significant changes were noticed in different outcomes with the exception of total cholesterol (−4.10%, p = 0.07). In the linear regression model, the intervention and the total number of clinic visits predicted HbA1c improvement.ConclusionsImplementation of a patient-specific integrated care program involving a multidisciplinary team approach, frequent clinic visits, and intensified insulin treatment was associated with marked improvement in glycemic control and cardiovascular risk factors of poorly controlled T2DM patients in a safe and reproducible manner.Trial registrationISRCTN Identifier: ISRCTN83437562 September 19, 2016 Retrospectively registered.

Earlier intensified insulin treatment of Type 1 diabetes and its association with long-term macrovascular and renal complications.

To investigate the incidence of all-cause mortality, composite mortality and morbidity in people with Type 1 diabetes formerly randomized in the Stockholm Diabetes Intervention Study. A total of 102 people with Type 1 diabetes were randomized in the period 1982-1984 to intensified conventional treatment or standard treatment with insulin for a mean of 7.5 years. We prospectively re-evaluated this cohort for the period until 2011 with regard to all-cause mortality and composite mortality, which consisted of myocardial infarction, stroke and end-stage renal disease as primary endpoints. Secondary endpoints were first-time hospitalization for myocardial infarction and stroke or end-stage renal disease. Data on HbA1c levels (mean of 22 values/person) were retrospectively collected between 1996 and 2011. During the median follow-up of 28 years, 22 people died: seven in the intensified conventional insulin group compared with 15 in the standard treatment group (P = 0.30). With regard to composite mortality, six people in the intensified conventional insulin group died compared with 11 in the standard treatment group (P = 0.56). For the secondary endpoints, 11 people in the intensified conventional insulin group developed myocardial infarction or stroke compared with 17 in the standard treatment group (P = 0.72), and one person in the intensified conventional insulin compared with seven people in the standard treatment group developed end-stage renal disease (P = 0.09). Mean HbA1c levels did not differ between groups during the follow-up years. All-cause mortality, cardiovascular morbidity and progression to end-stage renal disease did not differ in people with Type 1 diabetes earlier randomized to intensified insulin treatment.

Disordered eating and insulin restriction in youths receiving intensified insulin treatment: Results from a nationwide population-based study.

This Germany-wide population-based study sought to estimate the prevalence of disordered eating and insulin restriction (IR) among 819 youths aged 11-21 years with early-onset type 1 diabetes (T1D) and a disease duration of at least 10 years. All respondents answered the five-item SCOFF screening questionnaire for eating disorders (EDs) and reported on the frequency of IR and clinical outcomes. Screening for disordered eating was positive when more than two SCOFF items were answered affirmatively. Frequent IR was defined as IR occurring more than five times per week. A total of 28.2%/9.2% of the female/male patients were SCOFF-positive without IR and 4.2%/5.3% reported frequent IR but were SCOFF-negative; 2.7%/1.9% screened positive for both disordered eating and IR. Patients with disordered eating, frequent IR, or both showed significantly worse glycemic control and partly more inpatient-treated diabetic ketoacidoses than patients who screened negative. Approximately one in three female and one in six male patients with early-onset long-duration T1D reported disordered eating and/or frequent IR. Because of their association with worse outcomes, both disordered eating and IR should be considered in T1D care irrespective of sex, age at onset, and diabetes duration.

Acute Bilateral Cataract in Type 1 Diabetes Mellitus.

We report a case of a 17-year old boy, who presented acute bilateral cataract and complete vision loss within six days, three months after the diagnosis of Type 1 Diabetes Mellitus (T1DM) under optimal metabolic control (HbA1c 6%). At presentation (HbA1c 10.4%) and after correction of diabetic ketoacidosis (pH 6.917) and the beginning of intensified insulin treatment with insulin glargine once daily and insulin aspart before meals,the patient underwent full ophthalmologic examination,which was completely normal. Only few cases with acute bilateral cataract - all relatively shortly after the diagnosis of T1DM - have been reported. Several hypotheses have been drawn but the exact mechanism of this phenomenon remains unclear. The interesting finding in our case was the clearly elevated insulin autoantibodies (IAA) at the time of cataract formation, negative however at presentation. The relation between the elevation of IAA and cataract formation should be further investigated in diabetic patients.

Intensified insulin treatment is associated with improvement in skin microcirculation and ischaemic foot ulcer in patients with type 1 diabetes mellitus: a long-term follow-up study.

We investigated skin microcirculation and its association with HbA1c and the incidence of ischaemic foot ulcer in patients with type 1 diabetes formerly randomised (1982-1984) to intensified conventional treatment (ICT) or standard treatment (ST) with insulin for a mean of 7.5years. We re-determined the skin microcirculation of 72 patients (ICT 35 vs ST 37) from the original Stockholm Diabetes Intervention Study with iontophoresis topically applied with the following vasoactive stimuli: acetylcholine (ACh) (endothelial-dependent vasodilatation), sodium nitroprusside (SNP) (endothelial-independent vasodilatation), and capsaicin (C-nociceptive-dependent vasodilatation). HbA1c levels (mean of 14 values/patient) were prospectively collected between 1990 and 1995 and tested for association with skin microcirculation. The patients were followed until first hospitalisation for an ischaemic foot ulcer or until 2011. During the median 28years of follow-up, three patients developed ischaemic foot ulcers in the ICT group compared with ten in the ST group (logrank, p = 0.035). At the time of iontophoresis, HbA1c was lower in the ICT group (median 57mmol/mol [minimum-maximum 40-79mmol/mol]) compared with the ST group (68mmol/mol [41-96mmol/mol], p < 0.01) (DCCT: ICT 7.4% [5.8-9.4%] vs ST 8.4% [5.9-10.9%]). Stimulated blood flow was higher in the ICT vs ST group with significantly increased perfusion units (PU) for: ACh (8.1 PU [4.6-24.7 PU] vs 5.3 PU [1.7-21.4 PU], p < 0.01); SNP (8.1 PU [2.2-20.1 PU] vs 5.6 PU [2.3-19.2 PU], p = 0.03); and capsaicin (5.0 PU [1.7-22.9 PU] vs 3.4 PU [1.5-8.4 PU], p < 0.01). HbA1c was associated with vasodilatation induced by ACh (b = -0.02, p < 0.01) and capsaicin (b = -0.02, p = 0.03). HbA1c was independently associated with ACh (b = -1.48, p < 0.01) and capsaicin-induced vasodilatation (b = -1.45, p < 0.01). Improved glycaemic control in patients with type 1 diabetes is associated with an improvement in skin microcirculation and with a lower incidence of ischaemic foot ulcers. ClinicalTrials.gov NCT01957930.

TRATAMIENTO EN ADULTOS CON DIABETES MELLITUS TIPO 1: ¿QUÉ VARIABLES IMPACTAN EN EL CONTROL GLUCÉMICO?

Objetivos: analizar modalidades terapéuticas en personas con diabetes mellitus tipo 1 (DM1) y su relación con el control glucémico.Resultados: 514 pacientes, edad 40,6±14,6 años, sexo femenino 55,1%, antigüedad DM1 17,4±12,0 años, media A1C 8,0±1,5 %, media glucemia de ayunas 147,2±69,1 mg/dl, frecuencia de automonitoreo 3,3±1,5 veces/día. El 38,8% presentó A1C&lt;7%, mientras el 60,9% tenía A1C &lt;8%.Insulinoterapia intensificada 75,1%; con bomba de infusión 8,6%, realizaba conteo de hidratos, 62,1%. La media de A1C fue 7,8±1,5% en el tratamiento intensificado y 8,4±1,7% en el tratamiento convencional (p=0,001). Presentó hipoglucemias en la última semana el 67%, siendo mayor en el grupo intensificado (p=0,0001).En regresión logística múltiple, el mejor control glucémico correlacionó con la realización de actividad física (p&lt;0,002), conteo de hidratos (p&lt;0,04), respetar horario de comidas (p=0,0001) y mayor frecuencia de automonitoreo (p=0,004).Conclusiones: El 38,8% presentó A1C&lt; 7%. La insulinoterapia intensificada se asoció a mejores niveles de A1C y con mayor frecuencia de hipoglucemias. El mejor control correlacionó con realización de actividad física, respetar el horario de comidas, el conteo de hidratos y mayor frecuencia de automonitoreo.

Glycation of the Complement Regulatory Protein CD59 Is a Novel Biomarker for Glucose Handling in Humans

Human CD59, an inhibitor of the membrane attack complex of complement, is inactivated by glycation. Glycation inactivation of CD59 enhances complement-mediated injury in target organs of diabetes complications. We hypothesized that circulating soluble glycated CD59 (GCD59) represents a novel biomarker of blood glucose handling and aimed to conduct human study protocols to test this hypothesis. DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: Using a newly developed ELISA, we measured circulating soluble GCD59 in samples from 3 separate human studies evaluating acute and chronic glucose handling and glucose responses to insulin therapy. Study 1 (normal vs diabetic subjects) evaluated the cross-sectional association between GCD59 and glycated hemoglobin (HbA1c) in 400 subjects with and without type 2 diabetes. Study 2 (oral glucose tolerance test [OGTT] in nondiabetics) evaluated whether fasting GCD59 independently predicted the 2-hour glucose response to an OGTT in 109 subjects without a diagnosis of diabetes. Study 3 (intensified insulin treatment) evaluated the effect of intensification of glycemic control with insulin on GCD59 in 21 poorly controlled individuals with diabetes. In study 1 (normal vs diabetic subjects), GCD59 was independently and positively associated with HbA1c in individuals with and without diabetes (β = 1.1, P < .0001 and β = 1.1 P < .001, respectively). In study 2 (OGTT in nondiabetics), a single GCD59 measurement independently predicted the results of the 2-hour OGTT (β = 19.8, P < .05) after multivariate modeling. In study 3 (intensified insulin treatment), intensification of glucose control with insulin resulted in a concomitant and parallel reduction of average weekly glucose and GCD59 within 2 weeks. We observed robust relationships between a single measurement of blood levels of GCD59 and both acute (2-hour OGTT) and chronic (HbA1c) measures of glucose handling. Lowering of GCD59 levels closely reflected lowering of average weekly glucose within 2 weeks. The role of GCD59 in the diagnosis, management, and vascular risk stratification in diabetes warrants further investigation.

Initiation and Gradual Intensification of Premixed Insulin Lispro Therapy Versus Basal ± Mealtime Insulin in Patients With Type 2 Diabetes Eating Light Breakfasts

We compared two strategies initiating and intensifying insulin treatment and tested for noninferiority of premixed insulin to basal ± mealtime insulin analog in patients eating light breakfasts. This randomized, open-label, 48-week study compared two algorithms. Up to three injections of insulin lispro mix 25 and/or insulin lispro mix 50 (premix; premixed insulin lispro) or basal insulin glargine plus up to three injections of insulin lispro (basal+; glargine + insulin lispro) were used in type 2 diabetic patients uncontrolled with oral antihyperglycemic medication and consuming <15% daily calories at breakfast. The hypothesis was to test noninferiority of premix to basal+ for glycemic control measured by HbA1c after 48 weeks, assessed using ANCOVA with a 0.4% margin. Patients (n = 344; 176 [51%] females; mean [SD] age 54.3 [8.8] years; BMI 29.4 [4.6] kg/m(2); baseline HbA1c 9.02 [0.97]%) were randomized to premix (n = 171) or basal+ (n = 173). In the per-protocol analysis (n = 230), least squares means (95% CI) end point HbA1c were 7.40% (7.15-7.65) and 7.55% (7.27-7.82) in respective arms. Between-treatment difference was -0.14% (-0.42 to 0.13), with noninferiority met. Significantly more patients in premix achieved HbA1c targets of <7.0% compared with basal+ (48.2 vs. 36.2%; P = 0.024). Self-monitored blood glucose profiles, body weight changes, total insulin doses, and overall hypoglycemia (65 vs. 60%) were similar in premix and basal+ (P = 0.494), except nocturnal episodes (34.3 vs. 23.7%; P = 0.018) were more common in premix. Both intensive insulin strategies improved glycemic control; however, final HbA1c levels were seen above those achieved in previous treat-to-target trials, likely due to the inadequate insulin titrations and probably due to the complexity of tested insulin regimens. A higher percentage of patients achieved target HbA1c <7% with multiple premixed insulins, but this treatment resulted in more nocturnal hypoglycemia than a basal-bolus regimen.