The effect of carbohydrate intake on glycaemic control in individuals with type 1 diabetes: a randomised, open-label, crossover trial.

Background: Few studies have examined the effects of lower carbohydrate diets on glucose control in persons with type 1 diabetes (T1D). The objective of the study was to investigate whether a moderate carbohydrate diet improves glucose control in persons with T1D. Methods: A randomised, multicentre, open-label, crossover trial over 12 weeks. There were 69 individuals assessed for eligibility, 54 adults with T1D and HbA1c ≥ 58 mmol/mol (7.5%) were randomised. Interventions were moderate carbohydrate diet versus traditional diet (30 vs 50% of total energy from carbohydrates) over four weeks, with a four-week wash-out period between treatments. Masked continuous glucose monitoring was used to evaluate effects on glucose control. The primary endpoint was the difference in mean glucose levels between the last 14 days of each diet phase. Findings: 50 individuals were included in the full analysis set with a mean baseline HbA1c of 69 mmol/mol (8.4%), BMI 29 kg/m2, age of 48 years, and 50% were female. The difference in mean glucose levels between moderate carbohydrate and traditional diet was -0.6 mmol/L, 95% CI -0.9 to -0.3, p < 0.001. Time in range increased during moderate carbohydrate diet by 4.7% (68 min/24 h) (95% CI 1.3 to 8.0), p = 0.008. Time above range (>10 mmol/L) decreased by 5.9% (85 min/24 h), 95% CI -9.6 to -2.2, p = 0.003. There were no significant differences in the standard deviation of glucose levels (95% CI -0.3 to 0.0 mmol/L, p = 0.15) or hypoglycaemia in the range <3.9 mmol/L (95% CI -0.4 to 2.9%, p = 0.13) and <3.0 mmol/L (95% CI -0.4 to 1.6%, p = 0.26). Four participants withdrew, none because of adverse events. There were no serious adverse events including severe hypoglycaemia and ketoacidosis. Mean ketone levels were 0.17 (SD 0.14) mmol/L during traditional and 0.18 (SD 0.13) mmol/L during moderate carbohydrate diet (p = 0.02). Interpretation: A moderate carbohydrate diet is associated with decreases in mean glucose levels and time above range and increases in time in range without increased risk of hypoglycaemia or ketoacidosis compared with a traditional diet in individuals with T1D. Funding: The Healthcare Board, Region Västra Götaland, The Dr P Håkansson Foundation and the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement [ALFGBG-966173].

'Striving for freedom or remaining with what is well-known': a focus-group study of self-management among people with type 1 diabetes who have suboptimal glycaemic control despite continuous subcutaneous insulin infusion.

INTRODUCTION: Continuous subcutaneous insulin infusion (CSII) treatment is beneficial for obtaining glycaemic control for many persons with type 1 diabetes mellitus (T1DM). Still, some individuals do not obtain improved HbA1C levels despite CSII treatment, and there is a lack of evidence regarding how psychosocial factors may influence glycaemic control. Thus, we aimed to explore the attitudes and experiences of self-management among people with T1DM and suboptimal glycaemic control despite CSII treatment. RESEARCH DESIGN AND METHODS: A qualitative inductive design was applied, and four FGDs were performed with 37 adult men and women of various ages and duration of T1DM. All participants had suboptimal glycaemic control despite CSII treatment. Transcripts were analysed using qualitative manifest and latent content analysis. RESULTS AND CONCLUSION: The themes Searching for freedom and flexibility and Preferring safety and the well-known illustrated the divergent psychosocial strategies adapted, which both resulted in suboptimal glycaemic control. The technical devices and their effects on glycaemic levels may be challenging to understand and adjust to fit people's lifestyles. The rapid advances of technology devices in diabetes care can potentially change peoples' lives, but is the educational support developing as fast? Multifaceted web-based education of high quality, including tailored support with a person-centred focus, is more important than ever before as the need for technical knowledge and understanding may put further disease burdens to patients with T1DM on CSII treatment.

Implementation of Empagliflozin in Patients with Diabetes Mellitus Type 2 and Established Cardiovascular Disease: Estimation of 5-Year Survival and Costs in Sweden.

INTRODUCTION: Cardiovascular disease (CVD) affects approximately 30% of patients with diabetes mellitus type 2 (T2D) and leads to increased morbidity, decreased survival and increased healthcare utilization. The aim of this study was to estimate the impact of treating these patients with the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on survival and healthcare utilization. METHODS: Actual survival and healthcare utilization data from a 5-year retrospective cohort study on patients with T2D and CVD in the Region of Östergötland, Sweden were used as a starting point. Actual data were adjusted in accordance with risk reductions for mortality and CV events related to empagliflozin treatment as reported in the EMPA-REG OUTCOME study. RESULTS: Applying the risk reductions related to empagliflozin treatment on the cohort of patients with T2D and CVD in Östergötland resulted in an increase in 5-year survival of 96 days per patient and reduced costs for healthcare and drugs other than empagliflozin. Including the cost of empagliflozin, treatment led to an increased net cost per patient of approximately SEK 18,000 over 5 years. CONCLUSION: Empagliflozin treatment would reduce mortality and healthcare utilization in the patient group. The treatment strategy should be considered cost-effective, supporting a broad implementation of empagliflozin for patients with T2D and established CVD, in line with current national and international guidelines.

Disease Burden and Healthcare Costs for T2D Patients With and Without Established Cardiovascular Disease in Sweden: A Retrospective Cohort Study.

INTRODUCTION: Type 2 diabetes (T2D) is a complex chronic disease with an increasing prevalence worldwide. It is commonly associated with complications, such as cardiovascular disease (CVD). Patients with both T2D and established CVD are exposed to increased risk of further cardiovascular events, which means increased healthcare costs and impairments to quality of life and survival. To determine the added burden of CVD for T2D patients, we have analyzed the consumption and costs of healthcare and mortality in two T2D patient cohorts, with and without established CVD, respectively, during a 5-year follow-up in a Swedish region. METHODS: Patients with T2D on 1 January 2012 were identified using the administrative database of Region Östergötland and the Swedish National Diabetes Register. Established CVD was defined as the presence of a CVD-related healthcare visit in the period 2002-2011. Identified T2D patients were then followed retrospectively for 5 years (2012-2016) and data collected on utilization of healthcare resources, healthcare costs, and survival. Data pertinent to the study were retrieved from regional databases and national registries. RESULTS: On the index date (1 January 2012) there were 19,731 patients with T2D (prevalence 4.5%) in Region Östergötland, of whom 5490 had established CVD. Those patients with established CVD were older, more often men, and had longer diabetes duration and worse kidney function than those without. Compared to T2D patients without CVD, those with CVD had a significantly higher healthcare consumption, experienced higher costs, and had lower survival during the follow-up. CONCLUSION: This study confirms that established CVD is common among patients with T2D (approximately 30%). Established CVD has negative effects on the utilization of healthcare resources, healthcare costs, and mortality. It is therefore very important to improve the treatment strategy of this patient group.

Comparisons of automated blood pressures in a primary health care setting with self-measurements at the office and at home using the Omron i-C10 device.

OBJECTIVE: We aimed to compare blood pressure (BP) levels recorded using the semiautomatic oscillometric Omron i-C10 BP device in patients with or without hypertension in three different settings: (a) when used by a doctor or a nurse at the office (OBP); (b) when used for self-measurement by the patient at the office (SMOBP); and (c) when used for 7 consecutive days at home (HBP). MATERIALS AND METHODS: A total of 247 individuals were invited to participate, but 78 of these individuals declined and a further seven were excluded, leaving a final cohort of 162 participants. RESULTS: The mean OBP was higher than HBP (difference 8.1±14/3.1±8.8 mmHg, P<0.0001) and so was SMOBP compared with HBP (difference 7.0±13/4.2±7.3 mmHg, P<0.0001). Sixteen participants (9.9%) had at least 10 mmHg higher systolic SMOBP than OBP and 28 (17%) participants had at least 10 mmHg lower systolic SMOBP than OBP. Participants who were current smokers had a larger mean difference between systolic OBP and SMOBP than nonsmokers (OBP-SMOBP in smokers: 6.6±9.4 mmHg, OBP-SMOBP in nonsmokers: 0.5±9.2 mmHg, P=0.011 between groups). CONCLUSION: Self-measurement of BP in the office does not preclude an increase in BP when levels in the individual patients are compared with HBP using the same equipment. Thus, SMOBP with a semiautomatic device does not lead to a reduction in the white-coat effect in the same manner as fully automatic devices.

Phases in development of an interactive mobile phone-based system to support self-management of hypertension.

Hypertension is a significant risk factor for heart disease and stroke worldwide. Effective treatment regimens exist; however, treatment adherence rates are poor (30%-50%). Improving self-management may be a way to increase adherence to treatment. The purpose of this paper is to describe the phases in the development and preliminary evaluation of an interactive mobile phone-based system aimed at supporting patients in self-managing their hypertension. A person-centered and participatory framework emphasizing patient involvement was used. An interdisciplinary group of researchers, patients with hypertension, and health care professionals who were specialized in hypertension care designed and developed a set of questions and motivational messages for use in an interactive mobile phone-based system. Guided by the US Food and Drug Administration framework for the development of patient-reported outcome measures, the development and evaluation process comprised three major development phases (1, defining; 2, adjusting; 3, confirming the conceptual framework and delivery system) and two evaluation and refinement phases (4, collecting, analyzing, interpreting data; 5, evaluating the self-management system in clinical practice). Evaluation of new mobile health systems in a structured manner is important to understand how various factors affect the development process from both a technical and human perspective. Forthcoming analyses will evaluate the effectiveness and utility of the mobile phone-based system in supporting the self-management of hypertension.

Impact of symptomatic hypoglycemia on medication adherence, patient satisfaction with treatment, and glycemic control in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to evaluate the impact of symptomatic hypoglycemia on medication adherence, satisfaction with treatment, and glycemic control in patients with type 2 diabetes based on the treatment goals stated in the Swedish national guidelines. METHODS: This cross-sectional, multicenter study was carried out between January and August 2009 in 430 consecutive primary health care patients on stable doses of metformin and sulfonylureas for at least 6 months. The patients completed questionnaires covering their experiences of low blood glucose and adherence, as well as barriers to and satisfaction with drug treatment (using the Treatment Satisfaction Questionnaire for Medication). Physicians collected the data from medical records. RESULTS: Patients who experienced moderate or worse symptoms of hypoglycemia reported poorer adherence to medication (46% versus 67%; P<0.01) and were more likely to perceive barriers such as "bothered by medication side effects" (36% versus 14%; P<0.001) compared with patients with no or mild symptoms. Patients with moderate or worse symptoms of hypoglycemia were less satisfied with their treatment than those with no or mild symptoms as determined by the Treatment Satisfaction Questionnaire for Medication-Global satisfaction (67.0 versus 71.2; P<0.05). Overall, achievement of target glycated hemoglobin (HbA1c) based on the treatment goals stated in the Swedish national guidelines was 40%. Despite poorer adherence, patients who experienced moderate or worse symptoms of hypoglycemia had lower mean HbA1c values than patients with no or mild symptoms (7.0% versus 7.3% [Diabetes Control and Complications Trial standard]; P<0.05). CONCLUSION: Symptomatic hypoglycemia in patients with type 2 diabetes on metformin and sulfonylureas was associated with nonadherence and decreased treatment satisfaction despite lower mean HbA1c values. A broader understanding of patient preferences and self-reported outcomes could improve the management of patients with type 2 diabetes.

A randomized cross-over trial of the postprandial effects of three different diets in patients with type 2 diabetes.

BACKGROUND: In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. OBJECTIVE: To study postprandial effects of three diets, during a single day, in NIDDM. METHODS: A low-fat diet (45-56 energy-% from carbohydrates), and a low-carbohydrate diet (16-24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32-35 energy-% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025-1080 kCal in men and 905-984 kCal in women. The test meals were consumed at a diabetes ward under supervision. RESULTS: Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (p<0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35 ± 2.2, of Mediterranean-style diet: 8.12 ± 5.2, p = 0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003). CONCLUSIONS: The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective. TRIAL REGISTRATION: ClinicalTrials.gov NCT01522157 NCT01522157.

QALY weights for diabetic retinopathy--a comparison of health state valuations with HUI-3, EQ-5D, EQ-VAS, and TTO.

OBJECTIVE: To estimate quality-adjusted life-year weights for patients with diabetic retinopathy by using various methods and to investigate the empirical validity of the different measures. METHODS: The study population comprised 152 patients with diabetes in Östergötland County, Sweden. Participants were interviewed by telephone by using the time trade-off (TTO) method and a visual analogue scale (EQ-VAS) (direct valuations) as well as the EuroQol five-dimensional questionnaire (EQ-5D) and the health utilities index mark 3 (HUI-3) (indirect valuations). The quality-adjusted life-year weights were adjusted for potential confounders by using analysis of covariance. The empirical validity of the measures was examined by testing their ability to detect hypothetical differences between severity levels of diabetic retinopathy and by investigating the correlation between the measures and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). RESULTS: All measures detected significant differences in scores between patient groups classified according to visual impairment in the better eye (analysis of covariance, P < 0.05), but only HUI-3 and EQ-VAS detected significant differences between patient groups classified according to visual impairment or pathological progression in the worse eye. HUI-3 recorded a difference of 0.43 in values between normal vision and blindness in the better eye, which was more than twice the differences captured by the other measures (0.15-0.20). In addition, HUI-3 showed the highest correlation with NEI VFQ-25 (r = 0.54; P < 0.001). CONCLUSIONS: In cost-utility analyses, the choice of quality-adjusted life-year measure may affect whether an intervention is considered cost-effective. Furthermore, if decisions are to be based on values from the general public, HUI-3 can be recommended for cost-utility analyses of interventions directed at diabetic retinopathy.

Self-reported experience of hypoglycemia among adults with type 2 diabetes mellitus (Exhype).

AIMS: To evaluate the experience of hypoglycemia in patients treated with metformin in combination with sulphonylureas (SUs) and the impact on patients' quality of life (QoL) and worry about hypoglycemia. METHODS: This was a national, cross-sectional, multicenter study. Patients with type 2 diabetes treated with metformin and SU dual therapy were recruited by 54 investigators between January 2009 and August 2009. The patients were asked to complete a QoL instrument, the EuroQol-5 Dimensions questionnaire (EQ-5D), and the Hypoglycemia Fear Survey (HFS-II). Investigators completed a web-based case report form on laboratory values, medical history and anti-diabetic treatment. RESULTS: A total of 430 patients (60% male) were included in the study. Mean age was 69 years. Approximately one fifth of the patients experienced moderate or worse symptoms of hypoglycemia. Patients who experienced moderate or worse hypoglycemia had lower QoL as measured by the weighted EQ-5D summary score (0.81 vs. 0.88; p<0.001) than patients who experienced mild or no hypoglycemia. CONCLUSIONS: Experience of hypoglycemia was found to be associated with lower QoL in patients with type 2 diabetes on dual treatment with metformin and sulphonylurea. This should be taken into consideration when selecting treatment for these patients in clinical practice.

Can diabetes medication be reduced in elderly patients? An observational study of diabetes drug withdrawal in nursing home patients with tight glycaemic control.

AIM: To explore the feasibility of withdrawal of diabetes medication in elderly patients with HbA1c