Ignite Creation Date:
2024-05-06 @ 7:12 PM
Last Modification Date:
2024-10-26 @ 3:03 PM
Study NCT ID:
NCT05939895
Status:
RECRUITING
Last Update Posted:
2024-02-20
First Post:
2023-07-03
Brief Title:
To Identify Anytime Hyperglycaemia in Subjects With Normoglycaemia and Prediabetes
Sponsor:
Diabetes Foundation India
Organization:
Diabetes Foundation India
Study Overview
Official Title:
To Identify Anytime Hyperglycaemia in Subjects With Normoglycaemia and Prediabetes
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To test these hypotheses The Investigators will recruit 100 overweight and obese adolescents with HbA1c ranging across the ADA classification spectrum from normal to prediabetesnearly 40normoglycemi 30 IFG 301GT measure free-living glucose by continuous glucose monitoring CGM and assess the relationships among CGM outcomes HbA1c and OGTT results FPG and 2-h glucose Individual with overt diabetes will be excluded
This will be a 2 visit study Subjects will be coming to Fortis CDOC after a minimum 8-hour overnight fast Informed written consent and validated questionnaire in a language known to them EnglishHindi will be obtained from all participants
Clinical details will be obtained from the case records of the patients Note of visible markers of insulin resistance acanthosis nigricans buffalo hump double chin subcutaneous fat pads skin Anthropometry skinfolds blood pressure will be recorded Overweight and obesity will be defined according to predefined guidelines for Asian Indian Abdominal obesity is defined as waist circumference of 90 centimetres cms in males and 80 cms in females
A blinded iPro Continuous Glucose Monitor Medtronic MiniMed Inc will be inserted After a calibration period of 1 hour fasting laboratory result will be collected FPG HbA1c HbA1c will be done by HPLC NGSP approved turbid inhibition immunoassay Then subjects will consume 175 gkg glucose maximum 75 g glucose beverage and will have a second venepuncture 2 hours later for plasma glucose measurement
While awaiting the 2-hour venepuncture participants will be provided instructions on CGM device care and calibration Participants will be instructed to wear the CGM device for a minimum of 72 hours and to not change any of their current dietary or activity habits for the period of CGM wear They will be trained to use a glucose monitor and collect capillary blood glucose values at least three times daily prior to meals Participants will also be asked to complete a simple log of their activity as well as record dietary intake and sleep and wake times The iPro and log-sheet will be returned in person after a minimum of 72 hours of recording time
Investigators and patients will be kept blinded to CGM recordings throughout the study Daily glycaemic variability will be assessed by the change in the mean amplitude of glucose excursions MAGE index and through the standard deviation SD of the mean 24-hour blood glucose concentration Day-to-day variability will be assessed through the mean of daily differences MoDD in mgdL Daily glycaemic control will be assessed by the mean M daily CGM value as well as by the times in minutesday spent in optimal glycaemic range 70-140 mgdL and above predefined hyperglycaemic thresholds 140 180 and 200 mgdL together with the corresponding area under the curve AUC values
In addition areas under 24-hour glycaemic traces AUCs will be analysed to estimate overall hyperglycaemia defined asAUC100 mgdL over the full 24-hour period AUCtotalpostprandial hyperglycaemia AUC0-4 h ie for four-hour periods after each of the main meals and if considered relevant by the core laboratory after additional snacks AUCpp and basal hyperglycaemia ie overall hyperglycaemia - postprandial hyperglycaemia AUCb
This will be a 2 visit study Subjects will be coming to Fortis CDOC after a minimum 8-hour overnight fast Informed written consent and validated questionnaire in a language known to them EnglishHindi will be obtained from all participants
Clinical details will be obtained from the case records of the patients Note of visible markers of insulin resistance acanthosis nigricans buffalo hump double chin subcutaneous fat pads skin Anthropometry skinfolds blood pressure will be recorded Overweight and obesity will be defined according to predefined guidelines for Asian Indian Abdominal obesity is defined as waist circumference of 90 centimetres cms in males and 80 cms in females
A blinded iPro Continuous Glucose Monitor Medtronic MiniMed Inc will be inserted After a calibration period of 1 hour fasting laboratory result will be collected FPG HbA1c HbA1c will be done by HPLC NGSP approved turbid inhibition immunoassay Then subjects will consume 175 gkg glucose maximum 75 g glucose beverage and will have a second venepuncture 2 hours later for plasma glucose measurement
While awaiting the 2-hour venepuncture participants will be provided instructions on CGM device care and calibration Participants will be instructed to wear the CGM device for a minimum of 72 hours and to not change any of their current dietary or activity habits for the period of CGM wear They will be trained to use a glucose monitor and collect capillary blood glucose values at least three times daily prior to meals Participants will also be asked to complete a simple log of their activity as well as record dietary intake and sleep and wake times The iPro and log-sheet will be returned in person after a minimum of 72 hours of recording time
Investigators and patients will be kept blinded to CGM recordings throughout the study Daily glycaemic variability will be assessed by the change in the mean amplitude of glucose excursions MAGE index and through the standard deviation SD of the mean 24-hour blood glucose concentration Day-to-day variability will be assessed through the mean of daily differences MoDD in mgdL Daily glycaemic control will be assessed by the mean M daily CGM value as well as by the times in minutesday spent in optimal glycaemic range 70-140 mgdL and above predefined hyperglycaemic thresholds 140 180 and 200 mgdL together with the corresponding area under the curve AUC values
In addition areas under 24-hour glycaemic traces AUCs will be analysed to estimate overall hyperglycaemia defined asAUC100 mgdL over the full 24-hour period AUCtotalpostprandial hyperglycaemia AUC0-4 h ie for four-hour periods after each of the main meals and if considered relevant by the core laboratory after additional snacks AUCpp and basal hyperglycaemia ie overall hyperglycaemia - postprandial hyperglycaemia AUCb
Detailed Description:
The worldwide prevalence of diabetes has increased dramatically over the past two decades and have reached epidemic proportions which is a global threat Diabetes in Asian Indians occurs one decade earlier and with more complications eg nephropathy cardiovascular disease than seen in other populations 1Furthermore Asian Indians with diabetes have more body fat abdominal adiposity and liver fat than white Caucasians even when non obese as categorised by body mass index BMI 2 India at present is contributing 72 million patients with diabetes 3 and in India there is an increasing trend of obesity and diabetes in younger population4 Prediabetes is a state of abnormal glucose homeostasis characterized by the presence of impaired fasting glucose impaired glucose tolerance or both Individuals with prediabetes are at increased risk for type 2 diabetes compared with individuals with normal glucose values The increased risk for cardiovascular disease in prediabetes is multifactorial with etiologies including insulin resistance hyperglycaemia dyslipidaemia hypertension systemic inflammation and oxidative stress 56 A major goal in the treatment of diabetes in youth is in the area of prevention Because most of the morbidity and mortality in diabetes arises from long-term complications early detection and prevention would be expected to have a tremendous beneficial human social medical and economic impact With these considerations in mind it is logical to intervene early with measures targeted to reverse specific pathophysiological defects present in the prediabetes state and that ultimately lead to development of overt diabetes78 The costs associated with diabetes and pre-diabetes challenge the financial integrity of our healthcare systems However screening would allow management aimed at preventing or delaying development of diabetes and complications and could possibly reduce costs
Recommendations regarding screening for pre-diabetes and diabetes have been made by the American Diabetes Association ADA but formal screening is infrequent Screening options include fasting plasma glucose FPG oral glucose tolerance tests OGTTs and glycosylated haemoglobin HbA1C 9 These mentioned tests have their share of pros and cons associated
Fallacies of glucose monitoring Hyperglycaemia as the biochemical hallmark of diabetes is unquestionable However fasting and 2-h OGTT gauge just a moment of a single day In addition the two assessments required to confirm diagnosis might be fallacious in describing a chronic and complex clinical condition Focussing only on morning glucose excursion might be facallious as this might miss glycaemic excursion at other time of the day with varying carbohydrate intake and insulin resistance Plasma glucose levels are not stable but rather vary throughout the day mainly in postprandial periods Fasting plasma glucose is altered by numerous factors like stress acute illness medication venous stasis posture sample handling food ingestion prolonged fasting and exercise 10 These factor are also likely affects the 2 hr OGTT Moreover most individuals do not pay attention to the request or are not asked to consume a diet with at least 200 g carbohydrate in the days before testing glucose Some individuals do not abstain from food in the 8 h before testing thus arriving to the laboratory in the postabsorptive rather than fasting condition The lack of appropriate preparation for glucose testing makes FPG OGTT less reliable for diabetes diagnosis with results sometimes falsely elevated and sometimes apparently normal Moreover stability of glucose measurement is always a major aspect to be considered in measuring FPG Glycolysis consumes glucose even in fluoride preservative for the first two hours after blood is collected and may continue up to 4 hrs This makes the accuracy of FPG and OGTT questionable
Fallacies of HbA1C The concentration of HbA1c in an individuals blood is proportional to the mean ambient levels of blood glucose over the lifespan of the red blood cell RBC ie 80-120 days
The A1C has several advantages compared with the FPG and OGTT including greater convenience fasting not required greater pre analytical stability and less day-to-day perturbations during stress and illness Although the use of HbA1c as a diagnostic tool is an attractive proposition its use for this indication in India at present is not practical because of the high cost of the test problems with standardization and poor availability of the test in certain parts of the country The HbA1C test with a diagnostic threshold of 65 48mmolmol diagnoses only 30 of the diabetes cases identified collectively using A1C FPG or 2-h PG 11 Iron-deficiency anaemia is endemic in India It is particularly common in adolescents as well as in women of the reproductive age group Hypo proliferative anaemias such as iron-deficiency anaemia prolong the lifespan of RBCs In addition malondialdehyde which is increased in iron-deficiency anaemia can enhance the glycation of Hb Both these factors can lead to falsely elevated HbA1CFew drugs such as DapsoneRibavirin antiretroviral agents and trimethoprim-sulfamethoxazole which are commonly used alter HbA1c levels by inducing hemolysis whereas hydroxyurea causes a shift from HbA to HbF causing an apparent fall in HbA1c levels Large doses of antioxidants such as vitamin C and vitamin E have also been reported to reduce HbA1c levels by interfering with Hb glycation
There are several other limitations to the use of HbA1c in assessing glycaemic control HbA1c levels can vary with age time of year and in the presence of conditions like uremia hyperbilirubinemia alcoholism and pregnancy Glycaemic variability has been shown to be independent risk factors of diabetes complication and HbA1C miss to capture this variability
Continuous glucose monitoring system CGMS
Continuous glucose monitoring CGM systems is an emerging technology that allows frequent glucose measurements every 5 min and the ability to monitor glucose trends in real time Although these devices are currently expensive and not widely used there is vast potential for their use in both the research and clinical territories Continuous glucose monitoring provides maximal information about shifting blood glucose levels throughout the day and facilitates the making of optimal treatment decisions for the diabetic patient For the treating clinician CGMS has the potential to improve detection of hypoglycaemia excursions as well as asymptomatic hypoglycaemia and the data to improve management of glucose levels in diabetes patients CGMS has tremendous potential to be used in high risk categories as well12 Accuracy of a CGMS Chen Z evaluated the accuracy of CGMS during OGTT in the detection of blood glucose changes in glucose in 49 out-patients with fasting plasma glucose of 39-110 mmolL The correlation indices between CGMS values and the VBG values during the entire OGTT and in phases of stable rapidly rising and falling glucose levels were 0928 0901 0924 and 0902 respectively P 0001 CGMS values showed good consistency with venous blood glucose values measured during OGTT confirming the efficiency of CGMS in detection the rapidly changing blood glucose during OGTT 12 He et al investigated 50 non-obese people with normal glucose tolerance NGT 23 to 68 years old normal blood pressures and lipid profile using a CGMS for three days 72 hThe 48 h MBG mean amplitude of glycaemic excursions MAGE largest amplitude of glycaemic excursions LAGE postprandial peak glucose PPG postprandial glucose excursion PPGE mean of postprandial glucose excursion MPPGE and absolute means of daily differences MODD were measured The CGMS values were significantly correlated with the capillary glucose measurements r 0761 P 0005 The post-breakfast post-prandial glycaemic excursions PPGE were lower than those of post-lunch and post-dinner P 001 and P 005 In 95 of the daytime the glucose levels fluctuated between 41 and 88 mmolL and 78 of the participants n 39 had hyperglycaemia BG 78 mmolL and 10 n 5 had asymptomatic hypoglycaemia BG 28 mmolL This study suggested that CGMS tests may be important for detecting asymptomatic hyperglycaemia and hypoglycaemia The NGT people have exhibited abnormal blood glucose values in CGMS revealing problems in people with normal range of blood glucose 13
The Investigators hypothesized that HbA1c and OGTT outcomes FPG and 2-hour glucose identify individuals with different patterns of glycaemic abnormality and that the OGTT misses the presence of chronic postprandial hyperglycaemia because obese people frequently consume more than a 75-g carbohydrate load in their home environment and HbA1C values underdiagnose many prediabetes in Indian scenario
Recommendations regarding screening for pre-diabetes and diabetes have been made by the American Diabetes Association ADA but formal screening is infrequent Screening options include fasting plasma glucose FPG oral glucose tolerance tests OGTTs and glycosylated haemoglobin HbA1C 9 These mentioned tests have their share of pros and cons associated
Fallacies of glucose monitoring Hyperglycaemia as the biochemical hallmark of diabetes is unquestionable However fasting and 2-h OGTT gauge just a moment of a single day In addition the two assessments required to confirm diagnosis might be fallacious in describing a chronic and complex clinical condition Focussing only on morning glucose excursion might be facallious as this might miss glycaemic excursion at other time of the day with varying carbohydrate intake and insulin resistance Plasma glucose levels are not stable but rather vary throughout the day mainly in postprandial periods Fasting plasma glucose is altered by numerous factors like stress acute illness medication venous stasis posture sample handling food ingestion prolonged fasting and exercise 10 These factor are also likely affects the 2 hr OGTT Moreover most individuals do not pay attention to the request or are not asked to consume a diet with at least 200 g carbohydrate in the days before testing glucose Some individuals do not abstain from food in the 8 h before testing thus arriving to the laboratory in the postabsorptive rather than fasting condition The lack of appropriate preparation for glucose testing makes FPG OGTT less reliable for diabetes diagnosis with results sometimes falsely elevated and sometimes apparently normal Moreover stability of glucose measurement is always a major aspect to be considered in measuring FPG Glycolysis consumes glucose even in fluoride preservative for the first two hours after blood is collected and may continue up to 4 hrs This makes the accuracy of FPG and OGTT questionable
Fallacies of HbA1C The concentration of HbA1c in an individuals blood is proportional to the mean ambient levels of blood glucose over the lifespan of the red blood cell RBC ie 80-120 days
The A1C has several advantages compared with the FPG and OGTT including greater convenience fasting not required greater pre analytical stability and less day-to-day perturbations during stress and illness Although the use of HbA1c as a diagnostic tool is an attractive proposition its use for this indication in India at present is not practical because of the high cost of the test problems with standardization and poor availability of the test in certain parts of the country The HbA1C test with a diagnostic threshold of 65 48mmolmol diagnoses only 30 of the diabetes cases identified collectively using A1C FPG or 2-h PG 11 Iron-deficiency anaemia is endemic in India It is particularly common in adolescents as well as in women of the reproductive age group Hypo proliferative anaemias such as iron-deficiency anaemia prolong the lifespan of RBCs In addition malondialdehyde which is increased in iron-deficiency anaemia can enhance the glycation of Hb Both these factors can lead to falsely elevated HbA1CFew drugs such as DapsoneRibavirin antiretroviral agents and trimethoprim-sulfamethoxazole which are commonly used alter HbA1c levels by inducing hemolysis whereas hydroxyurea causes a shift from HbA to HbF causing an apparent fall in HbA1c levels Large doses of antioxidants such as vitamin C and vitamin E have also been reported to reduce HbA1c levels by interfering with Hb glycation
There are several other limitations to the use of HbA1c in assessing glycaemic control HbA1c levels can vary with age time of year and in the presence of conditions like uremia hyperbilirubinemia alcoholism and pregnancy Glycaemic variability has been shown to be independent risk factors of diabetes complication and HbA1C miss to capture this variability
Continuous glucose monitoring system CGMS
Continuous glucose monitoring CGM systems is an emerging technology that allows frequent glucose measurements every 5 min and the ability to monitor glucose trends in real time Although these devices are currently expensive and not widely used there is vast potential for their use in both the research and clinical territories Continuous glucose monitoring provides maximal information about shifting blood glucose levels throughout the day and facilitates the making of optimal treatment decisions for the diabetic patient For the treating clinician CGMS has the potential to improve detection of hypoglycaemia excursions as well as asymptomatic hypoglycaemia and the data to improve management of glucose levels in diabetes patients CGMS has tremendous potential to be used in high risk categories as well12 Accuracy of a CGMS Chen Z evaluated the accuracy of CGMS during OGTT in the detection of blood glucose changes in glucose in 49 out-patients with fasting plasma glucose of 39-110 mmolL The correlation indices between CGMS values and the VBG values during the entire OGTT and in phases of stable rapidly rising and falling glucose levels were 0928 0901 0924 and 0902 respectively P 0001 CGMS values showed good consistency with venous blood glucose values measured during OGTT confirming the efficiency of CGMS in detection the rapidly changing blood glucose during OGTT 12 He et al investigated 50 non-obese people with normal glucose tolerance NGT 23 to 68 years old normal blood pressures and lipid profile using a CGMS for three days 72 hThe 48 h MBG mean amplitude of glycaemic excursions MAGE largest amplitude of glycaemic excursions LAGE postprandial peak glucose PPG postprandial glucose excursion PPGE mean of postprandial glucose excursion MPPGE and absolute means of daily differences MODD were measured The CGMS values were significantly correlated with the capillary glucose measurements r 0761 P 0005 The post-breakfast post-prandial glycaemic excursions PPGE were lower than those of post-lunch and post-dinner P 001 and P 005 In 95 of the daytime the glucose levels fluctuated between 41 and 88 mmolL and 78 of the participants n 39 had hyperglycaemia BG 78 mmolL and 10 n 5 had asymptomatic hypoglycaemia BG 28 mmolL This study suggested that CGMS tests may be important for detecting asymptomatic hyperglycaemia and hypoglycaemia The NGT people have exhibited abnormal blood glucose values in CGMS revealing problems in people with normal range of blood glucose 13
The Investigators hypothesized that HbA1c and OGTT outcomes FPG and 2-hour glucose identify individuals with different patterns of glycaemic abnormality and that the OGTT misses the presence of chronic postprandial hyperglycaemia because obese people frequently consume more than a 75-g carbohydrate load in their home environment and HbA1C values underdiagnose many prediabetes in Indian scenario
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None