Annual Oral Glucose Tolerance Test Research Articles

The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study

ObjectiveDysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet β-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. Research design and methodsIResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. ResultsHigher IResp was associated with poorer performance on the DSST (−0.69 points per 100 unit increase in IGI, 95 % CI: −1.37, −0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. ConclusionsThese results suggest that a greater β-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.

Novel time-saving OGTT sparing HbA1c-HOMA2 based algorithm for the diagnosis of cystic fibrosis-related diabetes

AimsThe diagnosis of cystic fibrosis-related diabetes (CFRD) faces several challenges. We propose a novel screening algorithm to alleviate the burden of cystic fibrosis (CF). MethodsThrough a retrospective cross-sectional single-centre study, HbA1c and HOMA2 indices were assessed in multiple models as alternative diagnostic tools from OGTT data. We sought to establish specific thresholds for CFRD screening with oral glucose tolerance test (OGTT) as gold standard. We evaluated various straightforward or sequential approaches, in terms of diagnostic accuracy while also quantify the potential reduction in OGTTs through these different methods. ResultsHOMA indices were recovered in 72 patients. We devised a composite index that combines HbA1c and HOMA-B: Diabetes Predicting Index in cystic fibrosis (DIPIc) = (HbA1c(%) × 3.455) – (HOMA-B(%) × 0.020) – 19.294. This index yields the highest screening accuracy according to receiver-operating characteristics curves. Using a stepwise algorithm that incorporates DIPIc decreases the requirement for annual OGTTs. A CFRD exclusion cutoff less than −1.7445 (sensitivity 98 %), in conjunction with a CFRD diagnostic threshold greater than 0.4543 (specificity 98 %) allows for 71 % OGTT sparing. ConclusionThe composite index DIPIc is a suitable, less invasive screening method for CFRD, which enables to avoid many OGTTs.

Association of Pseudomonas aeruginosa incident infections with adherence to cystic fibrosis foundation care guidelines

BackgroundCare guidelines for cystic fibrosis (CF) have been developed to enhance consistent care and to improve health outcomes. We determined if adherence to CF care guidelines predicted P. aeruginosa incidence rates (Pa-IR) at U.S. CF centers in 2018. MethodsThis cross-sectional CF Foundation Patient Registry study included 82 adult and 132 pediatric centers. Adherence to 12 guidelines was defined categorically (guideline met) or as a continuous measure (proportion of patients being treated/evaluated per guideline). Association of adherence to individual guidelines with Pa-IR, accounted for center and patient characteristics relevant to Pa-IR and were modeled using random forests and weighted-least-squares (WLS) analyses. ResultsThe mean Pa-IR was 0.2 cases/patient-years at risk (SE 0.0074) for all centers combined. Guideline adherence was lowest for ≥4 bacterial cultures/year (54% of centers) and annual oral glucose tolerance test (OGTT) (48% of centers), and highest for annual non-tuberculous mycobacteria (NTM) sputum culture (98%). The mean number of guidelines met was 6.7 and higher for pediatric (7.3) than adult (5.6) centers, (p<0.001). The number of guidelines met correlated negatively with Pa-IR (β=-0.007, p = 0.043). Macrolide prescription and annual OGTT per guideline were associated with lower and higher Pa-IR, respectively. Centers with lower center-wide lung function, higher proportion of pwCF with low body-mass index, and location in the Southwest had higher Pa-IR. ConclusionOverall adherence to guidelines was high except for performing ≥4 bacterial cultures/year and OGTT. Higher Pa-IR was associated with center characteristics and lower guideline adherence. The lower Pa-IR with greater adherence to guidelines suggests that focusing on quality care can positively impact Pa-IR.

537 Increasing annual oral glucose tolerance test adherence by routine screening and on-site testing

537 Increasing annual oral glucose tolerance test adherence by routine screening and on-site testing

413 Increasing annual oral glucose tolerance test completion in children

413 Increasing annual oral glucose tolerance test completion in children

342-OR: The Impact of Insulin Secretion and Insulin Sensitivity on Cognition in Adults with Prediabetes—The Diabetes Prevention Program Outcomes Study (DPPOS)

Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant of dysglycemia, impaired insulin sensitivity (ISens) or insulin secretion (ISecr), or both, contributes to poorer cognitive function is not established. Among 1,054 adults with prediabetes (PreD) from the DPPOS, who did not develop diabetes, we investigated the relationship between ISecr, ISens and cognitive function, hypothesizing that lower ISens and/or lower ISecr is associated with worse cognition. Early ISecr was estimated by the mean insulinogenic index (IGI; pmol/mmol) from repeated annual oral glucose tolerance tests and ISens was estimated by the mean 1/fasting insulin from repeated fasting blood draws. ISecr and ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and processing speed (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Separate linear regression models were run for each cognitive outcome. Models included both mean ISecr and mean ISens as the main predictor variables and were adjusted for demographic, lifestyle, cardiovascular factors, and medications. Contrary to our hypothesis and to prior studies, higher mean ISecr was associated with poorer performance on the DSST (-0.74 points per SD increase in IGI, 95% CI: -1.43, -0.05; p=0.03). Mean ISens was not associated with DSST, nor were mean ISecr or mean ISens associated with SEVLT. These results suggest that higher insulin secretion in people with longstanding PreD may negatively impact processing speed, a critical component of executive control. This relationship could reflect a compensatory response of insulin in people with worsening metabolic dysregulation, who may also have poorer cognition. Further study is needed to replicate these findings and to understand the role of insulin in cognitive function. Disclosure A. Shapiro: None. A.H. Tjaden: None. S. Edelstein: None. S.E. Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc. Other Relationship; Novo Nordisk. P. Srikanthan: None. W.C. Knowler: None. E.M. Venditti: None. S. Golden: Advisory Panel; Abbott Diabetes, Medtronic. O. Carmichael: Research Support; Eli Lilly and Company. Advisory Panel; Novo Nordisk. Research Support; Nestlé Health Science. K.M. Gadde: Research Support; BioKier, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. J.A. Luchsinger: Consultant; Merck KGaA. Other Relationship; Wolters Kluwer Health. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)

P308 Strategies for the screening of glucose tolerance abnormalities and diabetes in people with cystic fibrosis: a French position statement

The increase in life expectancy of people with cystic fibrosis (pwCF) has come with new comorbidities, particularly diabetes. Cystic fibrosis related diabetes is a major challenge in the care of (pwCF) because it is a morbidity and mortality factor at all stages of the disease. Early glucose tolerance abnormalities observed from childhood are also associated with a poor pulmonary and nutritional outcome. This justifies systematic screening with an annual oral glucose tolerance test (OGTT) from the age of 10 years.

OR13-6 Deep learning-based voice screening technique for cystic fibrosis related diabetes

Abstract Background Cystic fibrosis-related diabetes (CFRD) is a unique type of diabetes that is associated with significantly increased morbidity and mortality in both children and adults with cystic fibrosis (CF). The prevalence of CFRD progressively increases with age such that more than half of adults with CF develop CFRD. Early diagnosis and treatment are associated with improvements in body weight and pulmonary function, reduction in the frequency of pulmonary exacerbations, and improved overall survival. Since patients with CFRD may present with no symptoms, screening is recommended starting from the age of 10 years with an annual oral glucose tolerance test (OGTT). Especially during the COVID-19 pandemic, requiring an in-person clinic visit can be challenging, which may lead to a delayed diagnosis of CFRD. Objectives The purpose of this project was to develop a state-of-the-art technique to detect changes in glucose levels of patients with CF by developing a deep learning-based audio classification tool. Preliminary work by our group suggested that voice characteristics could distinguish between patients with CFRD patients and patients with CF but without CFRD. We hypothesize that high blood glucose levels may cause laryngeal soft tissue swelling leading to changes in voice characteristics. Methods We performed a prospective cross-sectional study in adult patients with CF recruited from Emory CF Clinic from March to December 2021. We recorded 5-second voice samples of a sustained /a/ vowel via a portable digital microphone. The spectrogram was extracted via the Mel frequency cepstral coefficient. The training to test the dataset ratio was 80: 20. 20% of the training dataset were randomly selected to serve as a validation dataset. We designed a convolutional neural network (CNN) architecture for CFRD patients’ voice classification. Results There were a total of 100 subjects consisting of 43 patients with CFRD and 57 patients with CF without diabetes. The male to female ratio was approximately 60: 40 in both groups. Patients with CFRD had similar mean age and mean BMI to patients without CFRD. There was a significantly higher point of care glucose level in CFRD patients. The mean duration of a CFRD diagnosis was 9 years and the mean HbA1c level was 7.26 in the CFRD group. The performance of the VGG model CNN classifier achieved 98.7% and 94.92% accuracy on training and validation datasets, respectively. On the test dataset, the model achieved 73.53% sensitivity 69.77% specificity and 71.43% accuracy. Conclusions We found a deep learning-based audio screening tool for CFRD could be potentially used as an alternative tool for screening in the CF community. A convolutional neural network algorithm demonstrated high sensitivity and specificity to adequately differentiate between patients with and without CFRD. Larger prospective studies are required to test this technology in patients with every form of diabetes. Presentation: Sunday, June 12, 2022 12:15 p.m. - 12:30 p.m.

Clinical practice versus guidelines for the screening of cystic fibrosis-related diabetes: A French survey from the 47 centers

This study aimed to analyze clinical practices concerning cystic fibrosis-related diabetes (CFRD) screening in France. A web-based questionnaire was distributed between December 1, 2020 and January 31, 2021 among 47 cystic fibrosis centers including pediatric, adult, and mixed units. In accordance with guidelines, 92.8% of CF centers performed annual oral glucose tolerance tests (OGTT). Overall, 86.3% of CF centers performed 1- and 2-hour blood glucose determinations following OGTT. The OGTT was conducted before 10 years of age in 73% of pediatric centers. Continuous glucose monitoring (CGM) and laboratory glycated hemoglobin were employed for CFRD screening in 86.5% and 50% of centers, respectively. CGM was carried out in 69% of centers after glucose tolerance abnormalities had been detected in OGTT. Most CF centers used OGTT and CGM for CFRD screening. Studies are required to assess CGM usefulness as a validated tool in CFRD screening.

A Randomized Controlled Clinical Trial of Lifestyle Intervention and Pioglitazone for Normalization of Glucose Status in Chinese with Prediabetes.

Aims Prediabetes has been proved as an important risk factor of both diabetes and cardiovascular disease (CVD). Previous studies have shown that both lifestyle intervention and pioglitazone may delay the development of diabetes in patients with prediabetes. However, no study has ever explored whether these interventions could revert prediabetes to normal glycemic status as the primary outcome. Interventions that may revert prediabetes back to normal glucose status would be of great clinical importance. Materials and Methods We conducted a randomized, multicenter, 2 × 2 factorial designed study to examine whether intensive lifestyle intervention and/or pioglitazone could revert prediabetes to normal glucose tolerance. The participants were followed up for three years unless they reverted to normal glucose state or developed diabetes at the annual oral glucose tolerance test (OGTT). Reversion to normal glucose tolerance was confirmed on the basis of the results of OGTT. Results In our study, 1945 eligible patients were ultimately randomized into four groups. In this three-year follow-up study, overall, 60.0%, 50.3%, 56.6% and 65.1% reverted back to normoglycemic state over 3 years of follow-up in the conventional lifestyle intervention plus placebo, intensive lifestyle intervention plus placebo, conventional lifestyle intervention plus pioglitazone, and intensive lifestyle intervention plus pioglitazone groups, respectively. Compared to the conventional lifestyle intervention plus placebo group, all the other three groups did not show any significant benefit in terms of reverting back to normoglycemic state. Conclusion In our study, for patients with prediabetes, neither intensive lifestyle intervention nor pioglitazone had led to a higher reversion rate to normal glucose state. Trail registration.http://www.chictr.org.cn: ChiCTR-PRC-06000005.

Cystic fibrosis-related diabetes: Prevalence, screening, and diagnosis

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.

Glucose Metabolism and Insulin Response to Oral Glucose Tolerance Test (OGTT) in Prepubertal Patients with Transfusion-Dependent β-thalassemia (TDT): A Long-Term Retrospective Analysis.

BackgroundGlucose dysregulation (GD), including prediabetes and diabetes mellitus (DM), is a common complication of transfusion-dependent β-thalassemia (TDT) patients. The prevalence increases with age and magnitude of iron overload, affecting a significant proportion of patients. According to the international guidelines, the development of GD is frequently asymptomatic. Therefore, an early diagnosis requires an annual oral glucose tolerance test (OGTT) in all TDT patients aged ten years or older.PurposeThis retrospective study aims to evaluate the prevalence of GD in a homogenous population of prepubertal TDT patients and to enhance understanding of the pathogenesis and progression of glucose homeostasis in this group of patients.MethodsA selected group of 28 TDT patients was followed for at least 10.3 years (range: 10.3 – 28.10 years) from prepubertal age (mean 11.0 ± standard deviation 1.1 years) to adulthood (28.7 ± 3.7 years). Glucose tolerance and insulin response to OGTT were assessed, and indices of β-cell function, insulin sensitivity, and insulin secretion were calculated.ResultsAt baseline, 18 TDT patients had normal glucose tolerance (NGT) and 10 had isolated impaired fasting glycemia (IFG), according to the American Diabetes Association (ADA) criteria. Compared to 18 healthy prepubertal controls (mean ± SD age: 10.9 ± 1.1 years), the fasting plasma glucose (FPG), basal insulin level, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were significantly higher in the group of TDT patients (p= 0.001, 0.01 and 0.012, respectively). At the last observation, 7/18 patients (38.8%) with NGT and 9/10 (90%) with IFG at baseline deteriorated; 3 female patients developed type 2 DM (1 from the NGT group and 2 from the IFG group). Compared to adult controls, TDT patients with NGT had a reduced oral disposition index (DI) (p= 0.006) but no significant difference in HOMA-IR and Matsuda index. Conversely, all insulin indices (HOMA-IR, MI, and DI) but one [insulinogenic index (IGI)] were statistically different in TDT patients with GD compared to controls.ConclusionThis study underlines the concept that the spectrum of glucose tolerance in TDT patients represents a continuum of glucose homeostasis disturbances and that prepubertal patients with IFG are at higher risk of developing a further deterioration of glucose metabolism with time. Moreover, it appears that one-third of adult TDT patients with normal fasting glucose may develop GD in the second-third decade of life. Thus, early intervention could help to prevent an expected further decline of glucose tolerance.

Use of hemoglobin A1c to identify dysglycemia in cystic fibrosis.

BackgroundCystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%–50% of people with CF eventually develop CF–related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states.ObjectiveTo determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs.MethodsThis retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states.ResultsMean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250).ConclusionThere is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.

Long-Term Follow-up of β-Transfusion-Dependent Thalassemia (TDT) Normoglycemic Patients with Reduced Insulin Secretion to Oral Glucose Tolerance Test (OGTT): A Pilot Study.

ObjectiveTo study the endocrine pancreas’ function in transfusion-dependent β-thalassemia (β-TDT) patients with a normal glucose tolerance test (NGT) and hypoinsulinemia. In addition, the prospective long–term follow-up using an annual oral glucose tolerance test (OGTT) to detect any abnormality of glucose metabolism.Patients and methodsSeven β-TDT patients (mean age 22.4 ± 4.2 years) with NGT and inadequate insulin response (hypoinsulinemia) to OGTT were referred for a second opinion to an Italian Centre.ResultsThe first-phase insulin response (FPIR), expressed as the sum of 1 and 3 minutes insulin, to intravenous glucose tolerance test (IVGTT), was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in five. The results were not associated with β-cell autoimmunity. After 43 ± 26 months (range 11 – 80 months) of follow-up, two patients developed impaired glucose tolerance (IGT), three both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline, the lowest value of the insulinogenic index (IGI: 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at the diagnosis of IFG, IGT, and DM. There was a significant inverse correlation between ISSI-2 and area under the curve plasma glucose (AUC-PG).ConclusionsThese data demonstrated, for the first time, progressive deterioration in glucose homeostasis in β-TDT subjects with NGT and hypoinsulinemia and that the ISSI-2 index may be a valuable parameter to identify patients at high risk for developing glucose dysregulation.

Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People With Coronary Heart Disease and Impaired Glucose Tolerance: Insights From the ACE Trial.

We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD). Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-h PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA1c, FPG, 2-h PG, BMI, estimated glomerular filtration rate, for IGT alone, for IGT + impaired fasting glucose, and for use of thiazides, ACE inhibitors [ACEis]/angiotensin receptor blockers [ARBs], β-blockers, calcium channel blockers, or statins). Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], P interaction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41). Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD.

Screening for cystic fibrosis-related diabetes and prediabetes: Evaluating 1,5-anhydroglucitol, fructosamine, glycated albumin, and hemoglobin A1c.

Dysglycemia is prevalent in cystic fibrosis (CF) but screening with annual oral glucose tolerance tests (OGTT) can be burdensome. We investigated alternate glycemic markers-hemoglobin A1c (HbA1c), 1,5-anhydroglucitol (1,5AG), fructosamine (FA), and glycated albumin (GA)-as screening tests for CF-related diabetes (CFRD) and pre-diabetes (CFPD) in youth with CF as defined by the gold-standard OGTT 2-hour glucose (2hG). Youth 10 to 18 years with CF had a 1,5AG, FA, GA, HbA1c, and 2-hour OGTT collected. Correlations between all glycemic markers and 2hG were evaluated. Area under the receiver operative characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting CFPD (2hG ≥ 140 mg/dL) and CFRD (2hG ≥ 200 mg/dL) were determined. Fifty-eight youth with CF were included (2hG < 140, n = 16; CFPD, n = 33; CFRD, n = 9; 41% male, mean ± SD age 14.2 ± 3.6 years, BMI z-score 0.0 ± 0.8, % predicted forced expiratory volume in 1 second [FEV1] 89.9 ± 15.1, % predicted forced vital capacity [FVC] 103.2 ± 14.6). ROC-AUC's for all alternate markers were low for CFPD (0.52-0.67) and CFRD (0.56-0.61). At a cut point of 5.5%, HbA1c had 78% sensitivity (95% CI: 0.45-0.94) and 41% specificity (95% CI: 0.28-0.55) for identifying CFRD, correlating to a ROC-AUC of 0.61 (95% CI: 0.42-0.8). All alternate markers tested demonstrate poor diagnostic accuracy for identifying CFRD by 2hG.

Markedly Delayed Insulin Secretion and a High Rate of Undetected Overt Diabetes Characterize Glucose Metabolism in Adult Patients with Cystic Fibrosis After Lung Transplantation

Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT). Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m2) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m2; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed. In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m2*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m2*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m2*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism. AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.

What is the Real Usefulness of Glycated Hemoglobin Levels for Diabetes Screening in Patients With Cystic Fibrosis?

What is the Real Usefulness of Glycated Hemoglobin Levels for Diabetes Screening in Patients With Cystic Fibrosis?

A peer-support lifestyle intervention for preventing type 2 diabetes in India: A cluster-randomized controlled trial of the Kerala Diabetes Prevention Program.

BackgroundThe major efficacy trials on diabetes prevention have used resource-intensive approaches to identify high-risk individuals and deliver lifestyle interventions. Such strategies are not feasible for wider implementation in low- and middle-income countries (LMICs). We aimed to evaluate the effectiveness of a peer-support lifestyle intervention in preventing type 2 diabetes among high-risk individuals identified on the basis of a simple diabetes risk score.Methods and findingsThe Kerala Diabetes Prevention Program was a cluster-randomized controlled trial conducted in 60 polling areas (clusters) of Neyyattinkara taluk (subdistrict) in Trivandrum district, Kerala state, India. Participants (age 30–60 years) were those with an Indian Diabetes Risk Score (IDRS) ≥60 and were free of diabetes on an oral glucose tolerance test (OGTT). A total of 1,007 participants (47.2% female) were enrolled (507 in the control group and 500 in the intervention group). Participants from intervention clusters participated in a 12-month community-based peer-support program comprising 15 group sessions (12 of which were led by trained lay peer leaders) and a range of community activities to support lifestyle change. Participants from control clusters received an education booklet with lifestyle change advice. The primary outcome was the incidence of diabetes at 24 months, diagnosed by an annual OGTT. Secondary outcomes were behavioral, clinical, and biochemical characteristics and health-related quality of life (HRQoL). A total of 964 (95.7%) participants were followed up at 24 months. Baseline characteristics of clusters and participants were similar between the study groups. After a median follow-up of 24 months, diabetes developed in 17.1% (79/463) of control participants and 14.9% (68/456) of intervention participants (relative risk [RR] 0.88, 95% CI 0.66–1.16, p = 0.36). At 24 months, compared with the control group, intervention participants had a greater reduction in IDRS score (mean difference: −1.50 points, p = 0.022) and alcohol use (RR 0.77, p = 0.018) and a greater increase in fruit and vegetable intake (≥5 servings/day) (RR 1.83, p = 0.008) and physical functioning score of the HRQoL scale (mean difference: 3.9 score, p = 0.016). The cost of delivering the peer-support intervention was US$22.5 per participant. There were no adverse events related to the intervention. We did not adjust for multiple comparisons, which may have increased the overall type I error rate.ConclusionsA low-cost community-based peer-support lifestyle intervention resulted in a nonsignificant reduction in diabetes incidence in this high-risk population at 24 months. However, there were significant improvements in some cardiovascular risk factors and physical functioning score of the HRQoL scale.Trial registrationAustralia and New Zealand Clinical Trials Registry ACTRN12611000262909.

Effects of Packed Red Cell Transfusion on Blood Glucose Concentrations in Beta Thalassemia Major (BTM) Ashort Presentations of Personal Experience

The most accurate method with which to evaluate altered glucose metabolism in patients with TM is still controversial. Even if the annual oral glucose tolerance test (OGTT) by the age of 10 years is the recommended method, a diagnosis of ’normal’ glucose tolerance during OGTT does not exclude abnormal postprandial glucose levels at home . There is now evidence that the OGTT method, evaluating fasting and 2-h post load glucose, may miss episodes of hyperglycaemia . Furthermore, the credibility of Hb A1c has been questioned because the hemoglobin composition of patients’ erythrocytes are considerably modified, due to regular and frequent transfusions. The results may be falsely increased or decreased depending on the proximity to transfusion, shortened erythrocyte lifespan and the assay used . It has been demonstrated recently that the continuous glucose monitoring system (CGMS) is a useful and valid tool in defining glucose metabolism in children and adults affected by TM with early glucose derangements . Indeed, the CGMS allows monitoring of glycaemic profiles throughout a period of 72 h for a total of 288 glycaemic registrations per day. It identifies glycaemic excursions and constitutes a valid device to understand the 24-h glycaemic trend and profiles. Rimondiet al. investigated the value of using CGMS in six TM patients with abnormal glucose homeostasis after an oral glucose tolerance test (OGTT) . Two-hour OGTT glucose values and CGMS fluctuations were classified as normal if < 7.8 mmol/l, impaired if 7.8 to 11.1 mmol/l, diabetic if > 11.1 mmol/l. The TM patients spent from 1 to 23% of the time with a blood glucose level from 7.8 to 11.1 mmol/l. we evaluate three patients with Beta Thalassemai major using CGMSPatient 1 A 15 year old male with TM presented with nocturia. His FBG was 5.6 mmol/L and OGTT showed a BG level at 2hrs of 8.5 mmol/l. His CGMS showed a diabetic range of BG after dinner and overnight. Based on this tracing, a basal insulin (Glargine) was prescribed at night. A satisfactory response was recorded by CGMS .Patient 2 A 14 year old girl with TM with no symptoms related to glycemic abnormalities. Her FBG was 4.9 mmol/L and an OGTT showed a BG level at 2 hrs of 6.9 mmol/L (IGT). CGMS tracing showed prolonged persistent hyperglycemia after lunch suggesting a need for prandial insulin to cover her carbohydrate load. Insulin aspart before lunch properly controlled her glycemia . Patient 3 A 13 year old boy with TM had a normal FBG (4.5 mmol/L) and OGTT (2h BG =7.6 mmo/l). Applying CGMS monitoring showed IGT state. Furthermore, the effect of packed red cell transfusion showed marked reduction of his BG before meals and overnight. This is the first case to document the rapid beneficial effect of blood transfusion on glycemia in patiens with Beta thalssemia Major Advances in TM care have led to improved survival and quality of life in patients with TM; however, many chronic endocrine diseases have emerged as a result of potential endocrine complications by routine screening and a high index of suspicion is imperative for patients with TM to receive timely treatment.Our results demonstrate that the CGMS is a useful method to detect the variability of glucose fluctuations and offers the opportunity for better assessment of glucose homeostasis in TM patients. Proper and early iron chelation or the use of intensive iron chelation in those with high iron load the new oral chelators have been shown to decrease or reversethese glycemic abnormalities.In addition, optimization of insulin therapy with the help of CGMS appears to be clinically useful and costeffective approach. DisclosuresNo relevant conflicts of interest to declare.