Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umea University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification +/- metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD1181 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5 alpha-THF + 5 beta-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction

Трансоральная тиреоид- и паратиреоидэктомия: серия наблюдений

ЩИТОВИДНОЙ ЖЕЛЕЗЫ БОЛЕЗНИПАРАЩИТОВИДНЫХ ЖЕЛЕЗ БОЛЕЗНИОКОЛОЩИТОВИДНЫХ ЖЕЛЕЗ БОЛЕЗНИЭНДОКРИННЫЕ ХИРУРГИЧЕСКИЕ ОПЕРАЦИИХИРУРГИЯ ЭНДОКРИННЫХ ЖЕЛЕЗТИРЕОИДЭКТОМИЯЭНДОСКОПИЧЕСКАЯ ТЕХНИКАПАРАТИРЕОИДЭКТОМИЯОКОЛОЩИТОВИДНОЙ ЖЕЛЕЗЫ УДАЛЕНИЕТРАНСОРАЛЬНЫЙ ДОСТУПТРАНСОРАЛЬНАЯ ХИРУРГИЯ ШЕИДЕРМАТОЛОГИЧЕСКИЙ ИНДЕКСКАЧЕСТВО ЖИЗНИЦель. Представить результаты собственной серии трансоральных операций у пациентов с заболеваниями щитовидной и околощитовидных желез. Материал и методы. Трансоральная операция выполнена 20 женщинам и 1 мужчине. Все пациенты оперированы по поводу первичного заболевания и соответствовали критериям отбора на основании ультразвукового и цитологического исследований, гормонального фона, соматического статуса. Показаниями к операции в 17 случаях явился узловой зоб, в 2 случаях – диффузный токсический зоб, в 2 случаях – первичный гиперпаратиреоз, аденома околощитовидной железы. Хирургическая техника включала в себя трехпортовый доступ в нижнем своде преддверия рта и газовый способ поддержания рабочей полости. Для операции использовались стандартные лапароскопические инструменты и ультразвуковое энергетическое устройство. В послеоперационном периоде пациенты прошли тест по субъективной оценке эстетического результата операции с использованием опросника дерматологического индекса качества жизни. Результаты. Тиреоидэктомия выполнена 4 пациентам, 15 пациентам – гемитиреоидэктомия и 2 пациентам – паратиреоидэктомия. У одной пациентки трансоральная паратиреоидэктомия выполнена в составе симультанной операции по поводу синдрома множественной эндокринной неоплазии 1 типа. У двух пациентов после операции верифицирован папиллярный рак T1N0M0. Среднее время операции составило 196,1 мин (диапазон 110 – 300 мин). Средняя кровопотеря 39,5 мл (диапазон 10 – 300 мл). На девятой по счету операции потребовалась конверсия вследствие неконтролируемого кровотечения. В одном случае отмечен преходящий парез возвратного гортанного нерва, в одном случае гематома. После операции медиана и среднее значение дерматологического индекса качества жизни составили 1 (0; 4) и 2,05 соответственно, что свидетельствует о незначительном влиянии на качество жизни. Заключение. Трансоральная эндоскопическая операция на щитовидной и околощитовидных железах перспективна в отношении оптимального выбора у пациентов, желающих избежать рубца на шее.Objective. To present the results of the author’s own series of transoral operations in patients with pathology of the thyroid and parathyroid glands. Methods. Transoral surgery was performed in women (n=20) and man (n=1). All patients were operated on for the primary disease and met the selection criteria based on ultrasound and cytological examinations, hormonal levels, and somatic status. Indications for surgery were: nodular goiter in 17 cases, diffuse toxic goiter – in 2 cases, parathyroid adenoma – in 2 cases. The surgical technique included a three-port approach in the lower fornix of the vestibule of the mouth and a gas technique for maintaining the working cavity. Standard laparoscopic instruments and an energy based ultrasonic device were used for the operation. In the postoperative period, patients underwent a test for subjective assessment of the aesthetic result of the operation using the survey of the dermatology life quality index. Results. Thyroidectomy was performed in 4 patients, hemithyroidectomy – in 15 patients and parathyroidectomy – in 2 patients. In one patient, transoralparathyroidectomy was performed as a part of a simultaneous operation for multiple endocrine neoplasia type 1 syndrome. Papillary cancer T1N0M0 was verified in two patients after surgery. The mean operation time was 196.1 min (range 110 – 300 min). Average blood loss – 39.5 ml (range 10 – 300 ml). The nineth operation required the conversion due to severe bleeding. In one case, the temporary recurrent laryngeal nerve (RLN) injury was reported, in one case – hematoma. After surgery, the median and average values of the dermatology life quality index were 1 (IQR 0-4) and 2.05, respectively, which indicates an insignificant effect on the quality of life. Conclusion. Transoral endoscopic surgery on the thyroid and parathyroid glands would be the promising optimal choice in patients to avoid scarring on the neck

Reduction in saturated fat intake for cardiovascular disease

BACKGROUND: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. OBJECTIVES: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. SEARCH METHODS: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. SELECTION CRITERIA: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. MAIN RESULTS: We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. AUTHORS' CONCLUSIONS: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events

Effekter av livsstilsförändring på hjärnfunktion och stresshormoner vid fetma och typ 2 diabetes

Background Obesity and associated metabolic dysregulation are linked to impaired cognitive function and alterations in brain structure, which increases the risk of age-related dementia. Increased glucocorticoid (GC) exposure may be a potential mediator of these negative effects on the brain. Methods and results In paper 1, we tested the relationship between cortisol levels, brain morphology and cognitive function in 200 women and men. Salivary cortisol levels were negatively related to cortical surface areas in prefrontal brain regions in both sexes. In participants with type 2 diabetes, high salivary cortisol levels were associated with lower memory performance. In paper 2, we tested in 70 overweight women the effects on tissue-specific GC metabolism of a Paleolithic diet or a diet following the Nordic nutrition recommendations. The 24-month interventions led to decreased expression of the GC-activating enzyme 11βHSD1 in adipose tissue, interpreted as a normalization of an obesity-related disturbance in GC metabolism. Furthermore, GC metabolism by 5α-reductase increased substantially after 2 years, an unexpected and novel result. The outcomes did not differ by diet. In paper 3, 20 women included in paper 2 were examined with functional magnetic resonance imaging (fMRI) while performing a memory task at baseline and after 6 months. Memory performance improved and functional brain responses increased in the hippocampus. Once again, the results were similar in both diet groups. In paper 4, 24 overweight participants with type 2 diabetes were examined with fMRI, using the same memory test as in paper 3, at baseline and after 12 weeks of intervention with a Paleolithic diet with or without exercise training. Functional brain response increased in the hippocampus, but memory was not improved. The addition of physical exercise did not alter the results. Conclusion Cortisol levels are linked to prefrontal brain structure and, at least in type 2 diabetes, lower memory performance. Furthermore, the dysregulated GC metabolism in obesity can be reversed by long-term diet- induced weight loss. Finally, dietary interventions with associated metabolic improvements alter functional brain responses during memory testing, including increased activation of the hippocampus. Whether these changes are linked to alterations in GC exposure and mediate improved cognition requires further study.

Patient's experience of surviving a cardiac arrest : a literature review

Hjärtstopp är den tredje vanligaste dödsorsaken i Europa och allt fler överlever hjärtstoppet men merparten drabbas av någon form av konsekvens, både fysiska och psykiska komplikationer. Det saknas uppdaterade sammanställningar av forskning som belyser de drabbades upplevelser av att ha överlevt ett hjärtstopp. Det behövs mer evidensbaserad kunskap för att optimera omhändertagandet av personerna som överlevt hjärtstopp och deras anhöriga.  Syftet är att belysa patienters upplevelser och erfarenheter av sin livssituation efter att ha överlevt ett hjärtstopp.  En allmän litteraturstudie med systematisk sökstrategi valdes som metod och artikelsökningar gjordes i databaserna PubMed, CINAHL och PsychInfo. Totalt valdes 15 artiklar ut till resultatet och dessa kvalitetsgranskades. Resultaten analyserades med integrerad analys där likheter och skillnader tydliggjordes som sedan formade totalt fyra kategorier och tolv underkategorier. Kategorierna kopplades löpande till Cullbergs kristeori. I resultatet presenteras kategorierna, mening och sammanhang, en förändrad kropp, existentiell påverkan och emotionella reaktioner. Personer som överlevt hjärtstopp har många och ibland motstridiga känslor. Deltagarna berättade om långvariga fysiska symtom som en konsekvens av hjärtstoppet. De kände inte igen sin kropp och upplevde att de inte kunde lita på kroppens förmåga. Begränsningarna gjorde dem nedstämda och otrygga. Personerna som överlevt hjärtstopp önskade att de hade fått mer information om vad de hade att vänta sig efter utskrivningen från sjukhuset.  Att överleva ett hjärtstopp är en livsomvälvande händelse. Personerna kan ställas inför många utmaningar under återhämtningen. Den förändrade livssituationen ledde för en del till en förändrad identitet och de hittade en ny roll i livet. Andra upplevde svårigheter att acceptera sin nya livssituation och önskade att återgå till livet som det var innan. Att använda Cullbergs kristeori gav oss en större förståelse kring hur kriser kan ge en förändrad livsbild. Personer kan behöva individanpassat stöd för att komma vidare i krisprocessen och därmed nå en acceptans för sitt nya liv. Cardiac arrest is the third most common cause of death in Europe and more and more people survive cardiac arrest. The majority suffer from some form of consequence, both physical and mental complications. There is a lack of updated summary of research that shed light on the persons' experiences of having survived a cardiac arrest. More evidence-based knowledge is needed to optimize the care of people who have survived cardiac arrest and their relatives. The purpose is to shed light on patients' experiences of their life situation after surviving a cardiac arrest. A general literature study with a systematic search strategy was chosen as the method and article searches were performed in the databases PubMed, CINAHL and PsychInfo. A total of 15 items were selected for the result and these were quality reviewed. The results were analyzed with an integrated analysis where similarities and differences were clarified, which then formed a total of four categories and twelve subcategories. The categories were continuously linked to Cullberg's crisis theory. The results present the categories, meaning and context, a changed body, existential influence and emotional reactions. People who have survived cardiac arrest have many and sometimes conflicting emotions. Participants reported prolonged physical symptoms as a consequence of cardiac arrest. They did not recognize their body and felt that they could not trust the body's ability. The restrictions made them depressed and insecure. The people who survived cardiac arrest wished they had received more information about what to expect after discharge from the hospital. Surviving a cardiac arrest is a life-changing event. People can face many challenges during recovery. The changed life situation led in part to a changed identity and they found a new role in life. Others experienced difficulties in accepting their new life situation and wanted to return to life as it was before. Using Cullberg's crisis theory gave us a greater understanding of how crises can give a changed life picture. People may need individualized support to move forward in the crisis process and thus reach an acceptance of their new lif

Patient's experience of surviving a cardiac arrest : a literature review

Hjärtstopp är den tredje vanligaste dödsorsaken i Europa och allt fler överlever hjärtstoppet men merparten drabbas av någon form av konsekvens, både fysiska och psykiska komplikationer. Det saknas uppdaterade sammanställningar av forskning som belyser de drabbades upplevelser av att ha överlevt ett hjärtstopp. Det behövs mer evidensbaserad kunskap för att optimera omhändertagandet av personerna som överlevt hjärtstopp och deras anhöriga.  Syftet är att belysa patienters upplevelser och erfarenheter av sin livssituation efter att ha överlevt ett hjärtstopp.  En allmän litteraturstudie med systematisk sökstrategi valdes som metod och artikelsökningar gjordes i databaserna PubMed, CINAHL och PsychInfo. Totalt valdes 15 artiklar ut till resultatet och dessa kvalitetsgranskades. Resultaten analyserades med integrerad analys där likheter och skillnader tydliggjordes som sedan formade totalt fyra kategorier och tolv underkategorier. Kategorierna kopplades löpande till Cullbergs kristeori. I resultatet presenteras kategorierna, mening och sammanhang, en förändrad kropp, existentiell påverkan och emotionella reaktioner. Personer som överlevt hjärtstopp har många och ibland motstridiga känslor. Deltagarna berättade om långvariga fysiska symtom som en konsekvens av hjärtstoppet. De kände inte igen sin kropp och upplevde att de inte kunde lita på kroppens förmåga. Begränsningarna gjorde dem nedstämda och otrygga. Personerna som överlevt hjärtstopp önskade att de hade fått mer information om vad de hade att vänta sig efter utskrivningen från sjukhuset.  Att överleva ett hjärtstopp är en livsomvälvande händelse. Personerna kan ställas inför många utmaningar under återhämtningen. Den förändrade livssituationen ledde för en del till en förändrad identitet och de hittade en ny roll i livet. Andra upplevde svårigheter att acceptera sin nya livssituation och önskade att återgå till livet som det var innan. Att använda Cullbergs kristeori gav oss en större förståelse kring hur kriser kan ge en förändrad livsbild. Personer kan behöva individanpassat stöd för att komma vidare i krisprocessen och därmed nå en acceptans för sitt nya liv. Cardiac arrest is the third most common cause of death in Europe and more and more people survive cardiac arrest. The majority suffer from some form of consequence, both physical and mental complications. There is a lack of updated summary of research that shed light on the persons' experiences of having survived a cardiac arrest. More evidence-based knowledge is needed to optimize the care of people who have survived cardiac arrest and their relatives. The purpose is to shed light on patients' experiences of their life situation after surviving a cardiac arrest. A general literature study with a systematic search strategy was chosen as the method and article searches were performed in the databases PubMed, CINAHL and PsychInfo. A total of 15 items were selected for the result and these were quality reviewed. The results were analyzed with an integrated analysis where similarities and differences were clarified, which then formed a total of four categories and twelve subcategories. The categories were continuously linked to Cullberg's crisis theory. The results present the categories, meaning and context, a changed body, existential influence and emotional reactions. People who have survived cardiac arrest have many and sometimes conflicting emotions. Participants reported prolonged physical symptoms as a consequence of cardiac arrest. They did not recognize their body and felt that they could not trust the body's ability. The restrictions made them depressed and insecure. The people who survived cardiac arrest wished they had received more information about what to expect after discharge from the hospital. Surviving a cardiac arrest is a life-changing event. People can face many challenges during recovery. The changed life situation led in part to a changed identity and they found a new role in life. Others experienced difficulties in accepting their new life situation and wanted to return to life as it was before. Using Cullberg's crisis theory gave us a greater understanding of how crises can give a changed life picture. People may need individualized support to move forward in the crisis process and thus reach an acceptance of their new lif

Overcoming the struggle of living with type 2 diabetes - diabetes specialist nurses and patients perspectives on digital interventions

BackgroundDiabetes self-management education and support (DSMES) is a cornerstone in the treatment of type 2 diabetes mellitus (T2DM). It is unclear whether delivering DSMES as a digital health intervention (DHI) might meet the needs experienced by patients with T2DM and diabetes specialist nurses (DSN) of the primary health care system in Sweden.MethodsFourteen patients with T2DM and four DSN participated in three separate focus groups: two groups comprised patients and one group comprised DSN. The patients discussed the questions: "What needs did you experience after your T2DM diagnosis?" and "How might these needs be met with a DHI?" The DSN discussed the questions: "What needs do you experience when treating a patient with newly diagnosed T2DM?" and "How might these needs be met with a DHI?". Furthermore, data were collected in the form of field notes from group discussions at a meeting including 18 DSNs working with T2DM in PHCCs. The discussions from focus groups were transcribed verbatim and analyzed together with the field notes from the meeting using inductive content analysis.ResultsThe analysis yielded the overall theme: "Overcoming the struggle of living with T2DM", which was summarized in two categories: "learning and being prepared" and "giving and receiving support". Important findings were that, for success, a DHI for DSMES must be integrated into routine care, provide structured, high-quality information, suggest tasks to stimulate behavioral changes, and provide feedback from the DSN to the patient.ConclusionThis study highlighted several important aspects, from the perspectives of both the patient with T2DM and the DSN, which should be taken into consideration for the successful development and use of a DHI for DSMES

Sex and age differences in the incidence of acute myocardial infarction during the COVID-19 pandemic in a Swedish health-care region without lockdown : a retrospective cohort study

Background The incidence of acute myocardial infarction has decreased during the COVID-19 pandemic, but sex and age differences in this change in incidence have not been tested. Thus, we aimed to compare the incidence of acute myocardial infarction in a health-care region in Sweden during the COVID-19 pandemic with previous years and to evaluate sex and age differences. Methods We did a retrospective, observational cohort study using data from a national registry of patients admitted to coronary care units in Sweden. All patients admitted to one of three hospitals in Region Jonkoping County with a diagnosis of acute myocardial infarction during the COVID-19 pandemic (March 1 to July 31, 2020) or reference period (March 1 to July 31, 2017-19) were included. The incidence of acute myocardial infarction (ST-elevation and non-ST-elevation) was calculated for both study periods. Participants were grouped according to sex and age (<70 years vs >= 70 years). The incidence and the incidence rate ratio (IRR) between the two study periods was calculated for each group and compared between groups using the Breslow-Day test. Findings The study included 1088 participants, 846 who were admitted for acute myocardial infarction during the reference period and 242 who were admitted during the COVID-19 pandemic period. The IRR of acute myocardial infarction for the COVID-19 period compared with the reference period was 0.85 (95% CI 0.73-0.98). The IRR for acute myocardial infarction was significantly lower among women aged 70 years or older (0.56 [0.40-0.78]) than among men aged 70 years or older (0.97 [0.77-1.23]; p=0.0074). Interpretation The incidence of acute myocardial infarction decreased predominantly among women aged 70 years or older during the COVID-19 pandemic. This highlights potential sex differences in health effects of the COVID-19 pandemic, which should be further elucidated. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Using a paleo ratio to assess adherence to paleolithic dietary recommendations in a randomized controlled trial of individuals with type 2 diabetes

This study is a secondary analysis of a randomized controlled trial using Paleolithic diet and exercise in individuals with type 2 diabetes. We hypothesized that increased adherence to the Paleolithic diet was associated with greater effects on blood pressure, blood lipids and HbA1c independent of weight loss. Participants were asked to follow a Paleolithic diet for 12 weeks and were randomized to supervised exercise or general exercise recommendations. Four-day food records were analyzed, and food items characterized as “Paleolithic” or “not Paleolithic”. Foods considered Paleolithic were lean meat, poultry, fish, seafood, fruits, nuts, berries, seeds, vegetables, and water to drink; “not Paleolithic” were legumes, cereals, sugar, salt, processed foods, and dairy products. A Paleo ratio was calculated by dividing the Paleolithic calorie intake by total calorie intake. A mul-tiple regression model predicted the outcome at 12 weeks using the Paleo ratio, group affiliation, and outcome at baseline as predictors. The Paleo ratio increased from 28% at baseline to 94% after the intervention. A higher Paleo ratio was associated with lower fat mass, BMI, waist circumference, sys-tolic blood pressure, and serum triglycerides at 12 weeks, but not with lower HbA1c levels. The Paleo ratio predicted triglyceride levels independent of weight loss (p = 0.046). Moreover, an increased monounsaturated/saturated fatty acids ratio and an increased polyunsaturated/saturated fatty acids ratio was associated with lower triglyceride levels independent of weight loss. (p = 0.017 and p = 0.019 respectively). We conclude that a higher degree of adherence to the Paleolithic diet recommendations improved fat quality and was associated with improved triglyceride levels independent of weight loss among individuals with type 2 diabetes