Frontiers in

DIABETES
Volume 5 | Issue 1

Volume 5 | Issue 1
 CONTENT
InTouch
Does Ramadan fasting have a beneficial role in reducing cardiometabolic
abnormalities and inflammation in diabetes?

Mobile apps improve medication adherence in type 2 diabetes mellitus(T2DM)

Bridge to Excellence
IDF-DAR guidelines: Diabetes and Ramadan

Diabetes Connect
Correlation between thyroid hormone levels and nonalcoholic fatty liver
disease in type 2 diabetic patients

Spotlight
A minimized measurement scheme for predicting HbA1c using SMBG data in
T2DM

Diabetes in Control
Regular self-monitoring of blood glucose reduces diabetes mellitus- related
comorbidities

Abbreviations: T2DM, Type 2 diabets mellitus, WC, waist circumference; HC, Hip circumference; BMI, body mass index;IL-6, Interleukin-6, CRP, C reactive protein ; HDL-C, High density lipoprotein cholesterol;
LDL-C, low-density lipoprotein cholesterol; NAFLD, Non-alcoholic fatty liver disease;T1D, type 1 diabetes; FLI, fatty liver index; fT4, free thyroxine;HCL, hepatocellular lipid content; TSH, Thyroid-stimulating
hormone; SMBG, self-monitoring of blood glucose; CGM, continuous glucose monitoring; HbA1c, hemoglobin A1c ; MAE, mean absolute error; R, relevance analysis; Ab, After breakfast; AD, After dinner; AL, After
Lunch; BB, before breakfast; BD, before dinner; BL, before lunch; BT, bedtime HCL,hepatocellular lipid ; 1H-MRS, proton magnetic resonance spectroscopy
InTouch
Does Ramadan fasting have a beneficial role in reducing cardiometabolic
abnormalities and inflammation in diabetes?
Reference: Aljahdali A et al. Impact of Ramadan Fasting on Cardiometabolic and Inflammatory Biomarkers among Saudi Adults with Diabetes. Curr Diabetes Rev. 2024 Jan 8.

During Ramadan, abrupt alterations in daily routines, physical activity, and food consumption impact glycemic
control and require modification of treatment plans.

To help patients manage their medical conditions, it is imperative to investigate how these changes affect
glycemic management and other metabolic profiles throughout Ramadan.

Study To investigate the association between Ramadan fasting and anthropometric measurements
Objective and cardiometabolic and inflammatory biomarkers in adults with diabetes

Study
N= 68 adults with diabetes (mean SD age 21 – 71 years)
Population

Study Method:
Pre-fasting (Time 1) Peri-fasting (Time 2)
N=68 N=68
2-3 months before Ramadan fasting At least 15 days after Ramadan fasting commences

Socio-demographic questionnaire Diet assessment

including medical history
Outcomes
Diet assessment
Anthropometric measurements
Outcomes
Cardiometabolic biomarkers
Anthropometric measurements
Inflammatory biomarkers
Cardiometabolic biomarkers

Inflammatory biomarkers

Results:
Approximately 1 kg reduction in body weight, 2 cm in waist circumference (WC), and 1.5 cm in hip circumference
(HC) during the Time 2 (peri-fasting) visit have been noted compared to the baseline values at Time 1
(pre-fasting).

An increase in serum high-density lipoprotein cholesterol (HDL-C) by 7.58% at Time 2 (peri-fasting) compared to
the baseline value at Time 1 (pre-fasting) has been recorded.

Ramadan fasting has been associated with a 51.72% reduction in serum interleukin 6 (IL-6) and a 47.22%
reduction in serum C-reactive protein (CRP).

The study demonstrates the impact of Ramadan fasting on anthropometric

measurements (body weight, WC, HC, and BMI) and cardiometabolic (glucose, total
cholesterol, HDL-C, LDL-C, and triglycerides) and inflammatory biomarkers (IL-6 and
CRP) in adults diagnosed with diabetes.

Ramadan fasting has been associated with increased HDL-C levels and decreased
anthropometric measurements and inflammatory cytokine levels, supporting the
beneficial role of Ramadan fasting in reducing cardiometabolic abnormalities and
inflammation in adults with diabetes.
Mobile Apps Improve Medication Adherence in Type 2 Diabetes Mellitus
Reference: Hakami AH et al. Effect of Mobile Apps on Medication Adherence of Type 2 Diabetes Mellitus: A Systematic Review of Recent Studies. Cureus. 2024 Jan; 16(1): e51791.

To manage type 2 diabetes mellitus (T2DM) and achieve the best possible clinical results, medication adherence
is essential.

Patients with asthma, heart disease, hypertension, and older people with coronary heart disease have all seen
improvements in drug adherence due to the widespread use of mobile apps.

Study
To assess the effect of a mobile app on medication adherence in patients with T2DM
Objective

Study
N= 527 participants from diverse geographic locations
Population

Results:
All included studies showed significant improvement in medication adherence with the use of mobile apps.

Moreover, studies showed improvements in glycated hemoglobin with mobile app-based interventions.

The overall average change in HbA1c for the intervention group was -0.664 compared to -0.103 for the control
group.

Study or Subgroup Experimental Control Mean difference Weight Mean difference Weight
Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI

Zhillan Huang 2019 0.3 1.6 22 0.8 2.4 19 4.9% -0.50[-1.77 ,-0.77]
Rian Adi Pamungkas 2022 -1.603 1.144 30 -0.313 2.605 30 7.3% 1.29[-2.31 ,-0.27]
Amreet Ral 2023 -0.69 0.92 30 -0.35 1.3 30 17.6% -0.34[-0.91 ,-0.23]
Potjana Poonprapai 2022 -0.97 1.61 78 -0.12 1.66 79 20.2% -0.85[-1.36 ,-0.34]
Yeoree Yang 2020 -0.63 0.07 145 -0.28 0.071 94 50.0% -0.35[-0.37 ,-0.33]

Total (95% CI)

Heterogeneity: Tau2 = 0.05; Chi2 = 6.99, OT = 4 (P = 0.14); I2=43%
Test for overall effect: Z = 3.46 (P = 0.0005) -4 -2 0 2 4
Test for subgroup differences: Not applicable Favours Unfavours [control]

Figure 1: Effect of mobile app-based interventions on HbA1c

Adapted from: Hakami AH et al.

Significant improvement in the six-item Morisky Medication Adherence Scale was reported among the intervention
group compared with the control group (P =0.02).

Mobile apps can deliver various features and functionalities (e.g., medication reminders) and educational materials
to help patients take their medications as prescribed and improve lifestyle modification.

Mobile apps are seamlessly accessible with features supporting self-monitoring, medication reminders, education,
and telehealth, which hold promise for improving medication adherence for various chronic diseases, including
T2DM.

Mobile app-based interventions hold promising potential for improving medication

adherence and enhancing glycemic control in individuals with T2DM.
Bridge to Excellence
IDF-DAR Guidelines: Diabetes and Ramadan
Reference: Hassanein M et al. Diabetes and Ramadan: Practical guidelines 2021. Diabetes Res Clin Pract. 2022 Mar:185:109185.

Q.1. For individuals on 3 or more drug combinations (insulin and Sulfonylureas, SU), how much reduction in the
dose of insulin is advised during Ramadan fasting?
A. 25-50%
B. 25-30%
C. 20-50%

Q2. These medications do not require treatment modifications during Ramadan fasting.

A. Acarbose
B. DPP-4 inhibitors
C. SGLT2 inhibitors
D. All the above

Q3. Patients with diabetes with a high-risk of microvascular complications who are still on Ramadan fasting,
should
A. Be monitored and have weekly reviews during Ramadan
B. Make a concerted effort to stay hydrated outside of fasting periods
C. Monitor electrolyte and creatinine levels
D. Avoid foods with high potassium or phosphorous content
E. All the above

(Please check answers on the last page)

Diabetes Connect
Correlation between thyroid hormone levels and non-alcoholic fatty liver disease in
type 2 diabetic patients
Reference: Saatmann N et al. Association of thyroid function with non-alcoholic fatty liver disease in recent-onset Diabetes. Liver International. 2024;44:27–38.

Non-alcoholic fatty liver disease (NAFLD) and hypothyroidism have been associated with type 2 diabetes (T2DM).

The relationship between thyroid function and NAFLD in diabetes is less clear.

Study To investigate associations between free thyroxine (fT4) or thyroid-stimulating hormone

Objective (TSH) and NAFLD in recent-onset diabetes

Study N= 1129 patients [recent-onset type 1 diabetes (T1D, n = 358), T2DM (n = 596) or without
Population diabetes (control) (n = 175)]

The fatty liver index (FLI) is a surrogate marker of hepatic steatosis and fibrosis, and the diagnostic performance of the FLI to identify steatosis was validated against measurement of hepatocellular lipid (HCL), by
proton magnetic resonance spectroscopy (1H-MRS) in people with and without recent-onset diabetes. To examine different degrees of steatosis risk, the whole cohort was divided into steatosis categories
according to established cut-offs of the FLI: values <30 (low steatosis risk category) rules out, while values ≥60 (high steatosis risk category) rule in steatosis, and values of 30–60 (intermediate steatosis risk
category) indicates the possible presence of steatosis.

Results:
The study reported that fatty liver index (FLI) was inversely related to free thyroxine (fT4) in T2DM (p < .01), but not
in control (p = .45) and T1D (p = .45).

A negative relationship between hepatocellular lipid content (HCL) and fT4 (p ≤ .05) was recorded.

T2DM within the high steatosis risk category had a lower fT4 than those in the low steatosis risk category (p < .01),
who had higher fT4 than those within the intermediate steatosis risk category (p < .05).

T2D FLI was associated with fT4 in males (p < .01), but not in females with T2DM
25 ** (p = 0.26).
*
20 FLI was associated with TSH in males (p < .05), but not in females with T2DM
(p = 0.45).
fT4 (pmol/L)

15
Only in females with T2DM, fT4 correlated negatively with HbA1c (p < .05), which
did not relate to fT4 or TSH in any other group.
10

fT4 was positively related to insulin sensitivity in all (p < .05) and male T2DM
5 (p < .01).

0 Control and T1D had no advanced fibrosis risk and the risk for advanced fibrosis
was <1% in T2DM.
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Thyroid-stimulating hormone (TSH) was associated positively with FLI only in male
r
te
in

Steatosis risk T2DM before (p < .05), but not after adjustments for age and BMI ( p = .30).

Figure 2: Free thyroxine levels in participants

and T2DM with different steatosis risk from fatty
liver index (FLI)
Box graph with whiskers for 10–90 percentile. *p < .05, **p < .01
Adapted from: Saatmann N et al.

In T2DM, a link between a higher risk of steatosis and reduced thyroid

function—mediated by insulin resistance and body mass, particularly in men is
observed; in T1D, however, this relationship is absent.

The findings underline the need for thyroid function screening as early as possible in
type 2 diabetes.
Spotlight
A minimized measurement scheme for predicting HbA1c using SMBG data in T2DM
Reference: Li A et al. A Minimized Measurement Scheme for Predicting HbA1c Using Discrete Self-Monitoring Blood Glucose Data Within 4 Weeks for People with Type 2 Diabetes. Diabetes technology &
therapeutics. 2024;26(2):1-9.

In diabetes self-management, monitoring blood glucose can effectively track blood glucose fluctuations and
reflect the real-time effects of diet, exercise, drugs, etc. on blood glucose levels.

The two primary glucose monitoring techniques are self-monitoring of blood glucose (SMBG) and continuous
glucose monitoring (CGM).

CGM is too expensive to be used extensively in clinical practice; in comparison, SMBG is less expensive, and
utilizing it to predict HbA1c is a more suitable choice.

To establish an accurate and robust calculation model for predicting hemoglobin A1c (HbA1c)
Study for people with type 2 diabetes (T2DM) by using the fewest discrete blood glucose values
Objective according to an irregular data set and propose an appropriate, cost-effective and scientific
scheme for routine blood glucose monitoring

Study Two independent data sets were used in this study

Population N= 2432 people with T2DM, ~420,000 irregular blood glucose values, and 10,000 HbA1c values

The data were structured and then fitted using a regularized extreme learning machine, and
Study
the results were evaluated based on indicators such as mean absolute error (MAE), root mean
Method
square error, and relevance analysis (R) value

HbA1c for the Nth time HbA1c for the Nth time

Pre-Sleeping

Post-Dinner

Pre-Dinner

........
Post-Lunch

Pre-Lunch

Pre-Breakast

Fasting Blood glucose values are green

m m-1 ........ 12 11 10 9 8 7 6 5 4 3 2 1
Merged Sequential values are blue
Simplifying

Postprandial Compensated sequential values are yellow

........

Fasting

28 27 ........ 12 11 10 9 8 7 6 5 4 3 2 1

Merging every two days

Postprandial
........

Fasting

28 27 ........ 12 11 10 9 5
8 7 6 4 3 2 1

Interpolation Compensation

Postprandial

Fasting

14 13 12 11 10 9 8 7 6 5 4 3 2 1

Figure 4: Self-monitoring of blood glucose structuring method designed in this study. Irregular blood glucose values were structured into two 14-value blood
glucose sequences after simplifying, merging, and interpolation compensation

HbA1c, hemoglobin A1c

Adapted from: Li A et al.
Calculation Method:
Considering the nonlinearity of a few discrete blood glucose values to represent blood glucose level and the
overfitting of the model, regular extreme learning machine (RELM) was finally used for fitting. The calculation model
is expressed by the following formula.
1
HbA1c = X LW
1+ e-H
where H =IW • P + B,
where IW and B mean the weight and bias, respectively, of hidden layers randomly generated in RELM; LW means the
weight of each node of the hidden layer of network training; P means the structured information after the input of
blood glucose information; and RELM adopts sigmod activation function.

Results:
The prediction model (R = 0.8029, MAE= 0.3179%) can meet the clinical requirement of predicting HbA1c in
non-extreme patients by measuring a minimum of 14 blood glucose values in 4 weeks.

In clinical practice, when there are no other special requirements for blood glucose measurement, daily blood
glucose monitoring can effectively monitor the blood glucose level at a low cost.

Accurate prediction in patients with non-extreme HbA1c can be obtained by flexibly measuring only seven
fasting blood glucose values and seven postprandial blood glucose values in 4 weeks, reducing the acquisition
cost of HbA1c, and proving that it is a discrete SMBG scheme that can accurately describe the overall blood
glucose level over time.

Using discrete self-monitoring of blood glucose data within 4 weeks for individuals
with T2DM, a simplified calculation model has been built to accurately and robustly
predict HbA1c.
Diabetes in Control
Case illustrating blood glucose monitoring in type 2 diabetes
Reference: Weinstock RS et al. The Role of Blood Glucose Monitoring in Diabetes Management. Available online at: https://www.ncbi.nlm.nih.gov/books/NBK566165/ 2. Bouchaud CC ey+t al. A Qualitative
Evaluation of a Plate-Method Dietary Self-Monitoring Tool in a Sample of Adults Over 50. Current Developments in Nutrition. 2023; 7 (2023):101975

Case history:
A.B, a 67-year-old woman who has lived with type 2 diabetes for
14 years

BMI: 32 kg/m2

Current HbA1C: 8.3%

• She has been using an online weight loss program and has been
focusing on using the plate method* at mealtimes

•Although she does eat pasta and other carbohydrate-containing

foods, she says her portion sizes are small

Current Medication:
• Metformin 1000 mg/day

• 24 units of insulin glargine, which she reports taking every night

at her 9:00 p.m. bedtime

She has been checking her fasting glucose levels several times per
week, and all her values have been <130 mg/dL.

Her A1C continues to be above the goal

What was recommended?

A “paired checking” structured approach to
blood glucose monitoring (checking her glucose
before and 2 hours after dinner nightly for
1 week)
*Recommended proportion of 3 food groups on a plate (a half-plate of vegetables and
fruits, a quarter-plate of whole grain foods, and a quarter-plate of protein foods) without
suggesting specific serving targets2

Follow-up:
A.B’s glycemic targets are 80-130 mg/dL before meals and <180 g/dL 2 hours after meals.

BB AB BL AL BD AD BT

Monday 131 255

Tuesday 128 181

Wednesday 125 281

Thursday 129 263

Friday 122 281

Saturday 118 259

Sunday 134 277

AB, after breakfast; AD, after dinner; AL, after lunch ,; BB, before breakfast; BD , before dinner; BL,before lunch; BT, bedtime.
Table 2: 1 week of paired checking of glucose values before and 2 hours after dinner (mg/dL)
What patterns do you see?
All A.B’s post-dinner glucose values are above her target of <180 mg/dL

What do you suggest?

A.B, needs more medication to manage her post-meal glucose excursions

Consider adding a glucagon-like peptide-1 receptor agonist to her regimen to assist with both weight loss and
glycemic management

Suggest using blood glucose monitoring to check before and after other meals to see if her glucose levels are
consistently out of range at any other times

Discussion:
Blood glucose monitoring has been fundamental for optimal diabetes self-management, and it will remain an
important tool for people with diabetes for years to come.

The recommended frequency of blood glucose monitoring should be individualized.

Pattern recognition, including identifying glycemic excursions related to eating, physical activity, stress, and
illness, is important and should be used to help direct treatment.

The use of structured blood glucose monitoring profiles, such as checking before and after meals, before and
after exercise, and at bedtime and fasting, can assist in adjusting food, physical activity, treatment regimens, and
medication dosing.

It will be easier to use blood glucose monitoring effectively and efficiently if counseling strategies are adopted
that emphasize the information, motivation, and behavioral skills that people with diabetes need to succeed.

These strategies should also include the use of negotiated, incremental, achievable goals that are elicited from
people with diabetes rather than from health care professionals.

Bridge to Excellence
Answers
1. A. 25-50%

For the use of a registered medical practitioner or a hospital or a laboratory only.

Individuals on 3 or more drug combinations, especially those on both insulin and SU should be considered at
increased risk of hypoglycemia. An approximate 25–50% reduction in the dose of insulin is advised,
depending on the subsequent risk score after risk stratification.

2. D. All the above

Antidiabetic drugs such as metformin, acarbose, Thiazolidinediones (TZDs), Glucagon-like peptide-1
receptor agonists (GLP-1 RAs) and Dipeptidyl peptidase-4 (DPP-4) inhibitors work in a glucose-dependent
manner and generally have a low risk of hypoglycemia. These drugs generally do not require any dose
modifications during Ramadan. It is recommended that the normal three-meal dosing be redistributed to
accommodate the eating patterns of iftar and Suhoor during Ramadan. SGLT2I does not require treatment
modifications during Ramadan; however, if an individual is on multiple medications, a review of the doses
should be made to avoid the risk of hypoglycemia. Increasing fluid intake during the non-fasting hours of
Ramadan is recommended.

3. E. All the above

Individuals with diabetes who have microvascular health issues or who insist on fasting against the advice of
HCPs must consider being carefully monitored, have weekly reviews during Ramadan, make a concerted
effort to stay hydrated outside of fasting periods, monitor electrolyte and creatinine levels at various points
IN-861

during Ramadan to ensure safe fasting is being conducted and whether they should continue. They should
avoid foods with high potassium or phosphorous content.
Date of preparation: Mar 2024

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