Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).

Clinical utility of point-of-care glucose testing in the assessment of gestational diabetes: Prospective cohort study.

OBJECTIVE: To assess the clinical utility of point-of-care (POC) capillary blood glucose (CBG) testing in the assessment of gestational diabetes mellitus (GDM) during oral glucose tolerance test (OGTT). DESIGN: Prospective cohort study. SETTING: Antenatal clinics at King's College Hospital. POPULATION: Women screened for GDM between March and June 2020. METHODS: The CBG was measured using the POC StatStrip® test and the venous plasma glucose (VPG) was measured by Roche analyser (Cobas 8000 c702). GDM was diagnosed based on the 2015 National Institute for Health and Clinical Excellence (NICE) Clinical Guideline criteria. The two methods were compared statistically using Analyse-It 5.40.2. MAIN OUTCOME MEASURES: Diagnostic sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the POC StatStrip® test, compared with VPG measured by reference laboratory method. RESULTS: A total of 230 women were included. The number and percentage of women with glucose concentrations above the GDM threshold using the POC StatStrip® test versus laboratory VPG measurement was 15 (6.5%) versus eight (3.4%) at fasting and 105 (45.6%) versus 72 (31.1%) at 2 h, respectively. The sensitivity and specificity values (and 95% CIs) for the POC StatStrip® test were 88% (52%-99%) and 97% (93%-98%) at fasting and 97% (91%-99%) and 79% (71%-84%) at 2 h, respectively. However, the specificity and the NPV for the POC StatStrip® test for concentrations of ≤5.0 mmol/L at fasting or <7.5 mmol/L at 2 h were 100%, and the sensitivity and the PPV for concentrations of >9.5 mmol/L at 2 h were 100%. CONCLUSIONS: In our cohort the POC measurement of CBG cannot entirely replace the laboratory method for the OGTT; however, it can be used to rule out/rule in GDM for glucose concentrations of ≤5.0 mmol/L at fasting or <7.5/>9.5 mmol/L at 2 h.

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial - study protocol.

BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes.

AIMS/HYPOTHESIS: Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention. METHODS: We conducted [15O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA). RESULTS: Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2 ± 35.5 vs 422.7 ± 237.1; neuroglycopenic scores, 34.8 ± 88.8 vs 478.9 ± 311.1; both p < 0.002). There were subtle differences (p < 0.005, k ≥ 50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia. CONCLUSIONS/INTERPRETATION: Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.

Onset of an Active Charcot Foot in a Person with Longstanding Type 1 Diabetes and Normal Vibration Perception Threshold-A Case Report.

Charcot neuro-osteoarthropathy (CNO), or Charcot foot, is a disabling complication of diabetes, which is poorly understood and frequently overlooked. We describe an atypical presentation of an active Charcot foot in a woman with a long-standing type 1 diabetes who did not exhibit loss of protective sensation (sensate to a 10-gram monofilament) or loss of vibration sensation. These standard measures of large nerve fibre function ruled out "classical" neuropathy. However, additional testing showed reduced sweat gland function most likely related to degeneration of c-fibres (small fibre neuropathy). This case raises the awareness that in addition to the "textbook" description, in diabetes, Charcot foot can develop in individuals with "minimal" or "no signs" of clinical neuropathy. The onset of active Charcot foot should be suspected in every person with diabetes and history of trauma even when foot and ankle x-rays are normal. Offloading should be initiated until the diagnosis is proven otherwise.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed (n = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving (n = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.

The gestational diabetes future diabetes prevention study (GODDESS): A partially randomised feasibility controlled trial.

OBJECTIVES: To assess the feasibility of an ante- and post-natal lifestyle intervention for women with gestational diabetes mellitus (GDM) to reduce type 2 diabetes risk. DESIGN: A partially randomised patient preference feasibility trial. SETTING: Diabetes antenatal clinics in two inner-London hospitals, UK. PARTICIPANTS: Pregnant women ≥18 years with a GDM diagnosis and pre-pregnancy body mass index of ≥25kg/m2. INTERVENTION: Participants in the intervention group were offered four motivational interview-based sessions (two antenatally and two postnatally, at 3 and 6 months postpartum), a WhatsApp support group, a FitBit and electronic self-help resources. OUTCOME MEASURES: Recruitment; retention; intervention dose received; data completion; adaptions; proportion achieving ≥5% weight loss; weight change, blood glucose; blood pressure; diet, physical activity, breastfeeding and depression. Clinical outcomes were measured at baseline and 6 months postpartum. RESULTS: 50 participants were recruited from 155 eligible women (32% recruitment rate). Thirty-four were recruited to the intervention group (23 following randomisation (RI-group) and 11 based on preference (PI-group)); and 16 to the control group (13 randomised (RC-group) and 3 preference (PC-group)). Attrition was 44% (n = 22/50). Forty-six percent (n = 6) of the intervention group (25% (n = 2) of the RI-group and 80% (n = 4) of the PI-group) achieved ≥5% weight loss compared to 8% (n = 1) in the control group (95% confidence interval (CI) -0.69 to 0.07). Mean weight change was -2.1kg±9.0 in the intervention group (0kg±5.4 in the RI-group and -5.4kg±13.0 in the PI-group) compared to +4.4kg±4.9 in the control group (RC +4.4kg ±5.3 and PC +4.7kg ±3.1, 95% CI -12.4 to 0.2). CONCLUSIONS: Recruitment was feasible, but strategies to improve retention are needed. The findings suggest the intervention can support women with GDM to lose weight. The observed weight loss was primarily in women who preferred the intervention. Therefore, future trials may need to adopt a preference design and consider factors associated with preference. TRIAL REGISTRATION: Trial registration: ISRCTN52675820 https://www.isrctn.com/ISRCTN52675820?q=ISRCTN52675820&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search.

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus.

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography-tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11-13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m2 with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m2 (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.

A role for placental kisspeptin in ß cell adaptation to pregnancy.

During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. Kisspeptin has been shown to stimulate insulin release, through its receptor, GPR54. The placenta releases high levels of kisspeptin into the maternal circulation, suggesting a role in modulating the islet adaptation to pregnancy. In the present study we show that pharmacological blockade of endogenous kisspeptin in pregnant mice resulted in impaired glucose homeostasis. This glucose intolerance was due to a reduced insulin response to glucose as opposed to any effect on insulin sensitivity. A ß cell-specific GPR54-knockdown mouse line was found to exhibit glucose intolerance during pregnancy, with no phenotype observed outside of pregnancy. Furthermore, in pregnant women circulating kisspeptin levels significantly correlated with insulin responses to oral glucose challenge and were significantly lower in women with gestational diabetes (GDM) compared with those without GDM. Thus, kisspeptin represents a placental signal that plays a physiological role in the islet adaptation to pregnancy, maintaining maternal glucose homeostasis by acting through the ß cell GPR54 receptor. Our data suggest reduced placental kisspeptin production, with consequent impaired kisspeptin-dependent ß cell compensation, may be a factor in the development of GDM in humans.

Pregnancy outcomes in women with previous gestational hypertension: A cohort study to guide counselling and management.

OBJECTIVES: In pregnant women with previous gestational hypertension: to compare the prevalence of preeclampsia as defined by the 2001 versus the 2014 International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria, to determine the rates of fetal growth restriction (FGR) as defined, not only by birthweight centile, but in combination with fetal ultrasound studies and, finally, to determine rates of other related outcomes such as gestational diabetes (GDM) and obstetric cholestasis (OC). STUDY DESIGN: This was a retrospective observational study based at the Antenatal Hypertension Clinic, Kings College Hospital, London. Routinely collected data of 773 women booked between 2011 and 2016 with a history of gestational hypertension was analysed. All women were normotensive at booking and those with chronic hypertension were excluded. MAIN OUTCOMES MEASURES: Hypertensive disorders of pregnancy (ISSHP-2014), FGR, GDM. RESULTS: Forty-nine percent developed one or more pregnancy complications, of which 72% were hypertensive disorders of pregnancy, 25.8% preeclampsia, 25% GDM and 19% FGR. Overall recurrence rate of preeclampsia was 12.5% (ISSHP-2014). Higher blood pressure and body mass index at booking were associated with higher risk of preeclampsia and GDM. Earlier gestation of previous hypertension was associated with higher risk of preeclampsia and FGR. The ISSHP-2014 compared to the 2001 guidelines classified 56% more women as having preeclampsia. CONCLUSION: Pregnant women with a history of gestational hypertension have a 49% chance of developing a complication related to a hypertensive disorder, GDM and OC. The rate of preeclampsia was more than doubled if the updated ISSHP-2014 definition was used.

The Endocrine and Metabolic Characteristics of a Large Bardet-Biedl Syndrome Clinic Population.

Context: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder in which previous reports have described obesity and a metabolic syndrome. Objective: We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects. Design: We performed a case-control study. Setting: This study was performed at a hospital clinic. Patients: Study patients had a clinical or genetic diagnosis of BBS. Main Outcome Measurements: Our study determined the prevalence of a metabolic syndrome in our cohort. Results: A total of 152 subjects were studied. Eighty-four (55.3%) were male. Mean (± standard deviation) age was 33.2 ± 1.0 years. Compared with age-, sex-, and body mass index-matched control subjects, fasting glucose and insulin levels were significantly higher in subjects with BBS (glucose: BBS, 5.2 ± 1.2 mmol/L vs control, 4.9 ± 0.9 mmol/L, P = 0.04; insulin: BBS, 24.2 ± 17.0 pmol/L vs control, 14.2 ± 14.8 pmol/L, P < 0.001). Serum triglycerides were significantly higher in subjects with BBS (2.0 ± 1.2 mmol/L) compared with control subjects (1.3 ± 0.8 mmol/L; P < 0.001), but total cholesterol, high-density lipoprotein, and low-density lipoprotein were similar in both groups. Systolic blood pressure was higher in the BBS group (BBS, 135 ± 18 mm Hg vs control subjects, 129 ± 16 mm Hg; P = 0.02). Alanine transaminase was raised in 34 (26.8%) subjects with BBS, compared with five (8.9%) control subjects (P = 0.01). The rate of metabolic syndrome, determined using International Diabetes Federation criteria, was significantly higher in the BBS group (54.3%) compared with control subjects (26% P < 0.001). Twenty-six (19.5%) of male subjects with BBS were hypogonadal (serum testosterone, 9.9 ± 5.3 mmol/L), but significant pituitary abnormalities were uncommon. Subclinical hypothyroidism was present in 24 of 125 (19.4%) patients with BBS, compared with 3 of 65 (4.6%) control subjects (P = 0.01). Conclusions: Insulin resistance and the metabolic syndrome are increased in adult patients with BBS compared with matched control subjects. Increased subclinical hypothyroidism in the BBS cohort needs further investigation.

Outpatient management of steroid-induced hyperglycaemia and steroid-induced diabetes in people with lymphoproliferative disorders treated with intermittent high dose steroids.

High dose steroids (HDS) are used in the treatment of haematological malignancies. The reported risk of steroid-induced diabetes (SID) is high. However, screening is not consistently performed. We implemented a protocol for detection and management of SID and steroid-induced hyperglycamia (SIH) in haematology outpatients receiving HDS. Eighty-three people were diagnosed with a lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three people without known diabetes were screened by HbA1c and random venous plasma glucose. All patients (n = 34) subsequently prescribed HDS checked capillary blood glucose (CBG) pre-breakfast and pre-evening meal. Treatment algorithms used initiation and/or dose titration of gliclazide or human NPH insulin, aiming for pre-meal CBG 5-11 mmol/l. Type 2 diabetes was identified in 4/53 people screened (7.5%). Of 34 people treated with HDS, 17 (44%) developed SIH/SID. All 7 people with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without known diabetes, 8 (30%) developed SID and 1 required insulin. Pre-treatment HbA1c was higher in people who developed SID compared to those that did not (p = 0.002). This is the first report of a SID/SIH detection and treatment protocol for use in people with lymphoproliferative disorders receiving intermittent HDS, demonstrating its feasibility and safety.

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study.

OBJECTIVE: Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. RESEARCH DESIGN AND METHODS: Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order. RYGB subjects repeated the studies with somatostatin infusion and basal insulin replacement. Fullness, sickness, and postscan ad libitum meal consumption were measured. Regional brain FDG uptake was compared using statistical parametric mapping. RESULTS: RYGB subjects had higher overall fullness and food-induced sickness and lower ad libitum consumption. Brain responses to eating differed in the hypothalamus and pituitary (exaggerated activation in RYGB), left medial orbital cortex (OC) (activation in RYGB, deactivation in NW), right dorsolateral frontal cortex (deactivation in RYGB and NW, absent in Ob), and regions mapping to the default mode network (exaggerated deactivation in RYGB). Somatostatin in RYGB reduced postprandial gut peptide responses, sickness, and medial OC activation. CONCLUSIONS: RYGB induces weight loss by augmenting normal brain responses to eating in energy balance regions, restoring lost inhibitory control, and altering hedonic responses. Altered postprandial gut peptide responses primarily mediate changes in food-induced sickness and OC responses, likely to associate with food avoidance.