Diagnosis, type 1 and type 2 diabetes prediabetes glycemic targets

1. Diagnosis, Type 1 and Type 2 Diabetes,
Prediabetes, Glycaemic Targets
(Assessment of glycemic control, A1c goals, fasting and postprandial goals).
Dr. Sanjay Agarwal, MD, FACE, FACP, FRSSDI
Head, Dept. of Medicine & Diabetes, Ruby Hall Clinic
Head, dept. of Diabetes, Obesity & Metabolic Diseases, Sahyadri Hospitals
Secretary-General, RSSDI
Advanced Course in
Diabetes Care
2023/2024

2. Learning Objectives
3
1. Classification of Diabetes
2. Diagnosis of Diabetes
- Type 1 Diabetes
- Type 2 Diabetes
` - Gestational Diabetes
- Monogenic Diabetes
- Other form of Diabetes
3. Prediabetes
4. Glycemic Targets
5. Importance of Good Control

3. • 541 million adults (20-79 years) have carbohydrate intolerance (1 in 9)
• 319 million adults (20-79 years) have impaired fasting glucose (1 in 18)
The Diabetes & Prediabetes Epidemic
Global Diabetes Statistics, IDF
The number of
diabetes is expected
to rise to 643
million by 2030 and
783 million by 2045.
IDF Diabetes Atlas 2021 – 10th edition www.diabetesatlas.org
US:
DM:37.3 M
India: DM 101 M
(40% underdiagnosed)

4. Projections for metabolic disease prevalence in India
ICMR-INDIAB-17, June 2023, Lancet Diabetes Endocrinol

5. Asian Indian Phenotype

6. Classification of Diabetes

7. S.No Category
1 Type 1 diabetes (T1DM)
2 Type 2 diabetes (T2DM)
3
Hybrid forms of diabetes:
- Slowly evolving immune-mediated diabetes in adults (previously termed LADA-latent
autoimmune diabetes of adults)
- Ketosis-prone T2DM (previously termed Flatbush diabetes)
4
Other specific types
- Monogenic diabetes (defects of beta-cell function or insulin action)
- Diseases of the exocrine pancreas
- Endocrinopathies
- Drug- or chemical-induced diabetes
- Infection-related diabetes
- Uncommon forms of immune-mediated diabetes
- Other genetic syndromes sometimes associated with diabetes
5
Unclassified diabetes
- A temporary category used when diabetes does not fit into any of the other categories
6
Hyperglycemia first detected during pregnancy
- Diabetes mellitus in pregnancy
- Gestational diabetes mellitus Hyperglycaemia first detected during pregnancy
Individuals
diagnosed with
diabetes should be
classified according
to the World Health
Organisation
classification
system.
Classification of Diabetes

8. 5 ‘subtypes’ from data-driven cluster analysis
Ahlqvist et al, Lancet D&E 2018
1: SAID severe autoimmune diabetes - GAD +ve
2: SIDD severe insulin-deficient diabetes - low HOMA-B, GAD -ve
3: SIRD severe insulin-resistant diabetes - high HOMA-IR & BMI
4: MOD moderate obesity-related diabetes - high BMI, lower HOMA-IR
5: MARD moderate age-related diabetes - older, lower BMI
Insulin
resistance
HbA1c BMI Age Insulin
secretion
+ GAD

9. Clustering of Type 2 Diabetes Identified In Indians
Prevalence [A] and hazards ratios [B] for microvascular complications across
different subgroups in the Indian population
Journal of The Association of Physicians of India ■ Vol. 69 ■ February 2021

10. • Cluster analysis is useful to identify possible groups but
does not identify different types of diabetes
• The proposed 5 subtypes are reproducible and differ in
diabetes progression and treatment response
• Simple patient features (age, sex, BMI, baseline HbA1c,
eGFR) are much more useful to predict progression and
select treatment

11. Diagnosis of Diabetes

12. Glycated hemoglobin (HbA1c)
1
• HbA1c testing can prevent short- and long-term complication risks in diabetes, thus regular HbA1c testing
can facilitate appropriate diabetes care.
• Other advantages of this assay include feasibility of performing irrespective of the prandial state and its
pre-analytical and analytical stability.
• HbA1c testing is found to be more efficient when used along with CGM.
HbA1c represents average blood glucose level of patients over the last 3 months
HbA1c advantages
• HbA1c measures blood glucose for the previous 3 months, so it may have a “delayed effect” in guiding
medication dose.
• HbA1c testing does not reveal day-to-day fluctuations of blood-glucose level, thus failing to detect the
extent of glycemic variability, hypoglycemia, and hyperglycemia.
• The level of HbA1c may not reflect glycemic control in some populations due to different rates of
glycation and life span of red blood cells.
HbA1c disadvantages
RSSDI 2023 Guidelines on Glucose Monitoring

13. Glycated hemoglobin (HbA1c)
1
• In patients with hemoglobinopathies, iron deficiency anemia and hematologic disorders like thalassemia,
HbA1c may be an unreliable measure resulting in over diagnosis or under diagnosis of
diabetes/prediabetes.
• The Indian Council of medical research (ICMR) guidelines recommend for HbA1c testing done via HbA1c
analyzers certified by National Glycosylation Standardization Program (NGSP).
• The lack of NGSP-certified laboratories is the main limitation in India.
• The reports generated by various laboratories using the same assay technique are not comparable in
absence of this standardization.
• The cost burden associated with HbA1c test (approximate cost ranging from Rs 266 to Rs 476 per test)
is another constraint.
HbA1c disadvantages
RSSDI 2023 Guidelines on Glucose Monitoring

14. 2
Monitoring
techniques
Recommended care for different conditions Limited care for different conditions
HbA1c
• Monitor blood glucose by measuring HbA1c using high-precision methods
standardized and aligned to the international reference values as per DCCT
standards
• Measure HbA1c every 3-6 months depending on level, stability of blood glucose
control, and changes in therapy
• Advise individuals with diabetes that maintaining an HbA1c <7.0% minimizes
the risk of developing complications
• It is important to consider hematological factors that can confound HbA1c levels
in people with diabetes as abnormal hemoglobin levels are known to affect
HbA1c values in a way that can significantly alter the results concerning
diabetes control
• HbA1c targets need to be individualized based on age, comorbidities and risk of
hypoglycemia
For patients on insulin
• A combination of HbA1c and SMBG helps achieve glycemic control.
For patients on OADs
• Consider each initiation or dose increase of OADs as a trial, monitoring the
response through glucose monitoring (HbA1c, FPG, PPG, or SMBG) every 2-3
months.
• Based on the available resources and clinical judgment, the frequency of
glucose monitoring can be decided by the treating physician
• In limited resource settings, diabetes control may need to be
based on measuring plasma glucose levels alone.
• Based on the available resources and clinical judgment,
the frequency of glucose monitoring can be decided by
the treating physician
RSDDI recommendations on frequency of HbA1c
Recommended care and limited care recommendations by RSSDI experts for frequency/timing of HbA1c.

15. Self-monitoring of blood glucose (SMBG)
1
• It is an invasive technique that involves finger pricking with a lancet device, taking small blood droplets
in the testing strip, and then inserting it into the glucose meter.
• Glucose reading is exhibited in the glucose meter within a few seconds and recorded manually in the
SMBG chart.
• These readings allow the patients to adjust their lifestyle and the physicians to adjust treatment.
• SMBG can be conducted in a structured way, which is a methodical way of measuring glucose levels
daily at predefined times to understand patient’s blood glucose pattern at regular intervals in a whole
day based on which the drug dose is adjusted.
• This structured SMBG is preferred over unstructured SMBG to understand the blood glucose pattern
at a regular basis.
SMBG is the most common form of blood glucose monitoring performed by patients or their caregivers
using a glucose meter at home

16. • SMBG is important for patients who are on insulin, or hypoglycemic drugs, or experiencing glycemic
fluctuations, or not achieving targeted glucose levels.
• It helps to identify acute hypoglycemia or hyperglycemia and thereby take proper action.
• The affordability, portability, ease of use, and reasonably accurate data are the advantages of SMBG.
SMBG advantages
• Inconvenience of use (particularly carrying glucose meter while traveling and is a cumbersome method)
and pain associated with finger pricking, due to which patients find difficulty in using this daily.
• The cost of the test strips (approximately Rs 660 to Rs1245 per 50 strips) and lancets (approximate cost
from Rs 105 to Rs 200 per 100 lancets) particularly for patients paying healthcare out-of-pocket, is
another major concern, especially in underdeveloped or developing countries.
• Time required for the fingertip wound to heal and risk of infection
• Reduced shelf life of test strips
• Inaccurate blood glucose readings associated with inappropriate storage of test strips or due to user
error.
SMBG disadvantages
Advantages and disadvantages of SMBG

17. Monitoring
techniques
Recommended care for different conditions Limited care for different conditions
SMBG
1. T1D
I. Adults: SMBG needs to be conducted 5 to 8 times/day.
II. Children: 5-8 times/day and should include pre-meal, post-meal
and bedtime levels
• Based on the available resources and clinical judgment, the
frequency of glucose monitoring can be decided by the treating
physician.
2. T2D on OADs
I. New onset DM/ uncontrolled DM/DM during acute illness
Patients on SU or meglitinides
• Should monitor at least 4 times/day and should include pre-prandial
and bedtime levels.
Patients on other OADs
• At least FBG on alternate days.
II. Stable/well-controlled DM
• At least 4 tests in a week on 4 consecutive days or on alternate days
(including an FBG and 3 post-prandial values).
• Based on the available resources and clinical judgment, the frequency
of glucose monitoring can be decided by the treating physician.
1. T1D
I. Adults: Should be conducted at least 2 times/day if glycemic control is
optimal.
II. More frequent monitoring is required if glycemic control is sub-optimal based
on the judgment of the treating physician.
III. Children: The consensus on recommended care needs to be followed if
there is government and NGO support for glucose monitoring in children with
T1D.
IV. SMBG should be performed at least 3 times/day if such support is not
provided.
• Based on the available resources and clinical judgment, the frequency of
glucose monitoring can be decided by the treating physician.
2. T2D on OADs
I. New onset DM/ uncontrolled DM/DM during acute illness
Patients on SU or meglitinides
• FBG should be performed at least on alternate days.
• Patients on other OADs
• Once a week FBG should be done at least.
II. Stable/well-controlled DM
• At least 4 tests in a month—at least 1 test/week (including a FBG and 3 post-
prandial values in a month).
• Based on the available resources and clinical judgment, the frequency of
glucose • monitoring can be decided by the treating physician.
Recommended care and limited care recommendations by RSSDI experts for frequency/timing of SMBG.
RSDDI recommendations on frequency of SMBG

18. 2
Recommended care and limited care recommendations by RSSDI experts for frequency/timing of SMBG.
Monitoring
techniques
Recommended care for different conditions Limited care for different conditions
SMBG
3. T2D on insulin or insulin +OADs
I. New onset DM/uncontrolled DM/DM during acute illness
• SMBG should be performed at least 4 times/day which should
include pre-prandial and bedtime levels
• Must check glucose level when hypoglycemia is suspected.
II. Stable/well-controlled DM
• FBG at least on alternate days.
• 4 tests in a week on 4 consecutive days or on alternate days
(including an FBG and 3 post-prandial values).
• Must check glucose level when hypoglycemia is suspected.
• Based on the available resources and clinical judgment, the
frequency of glucose monitoring can be decided by the treating
physician.
3. T2D on insulin or insulin +OAD
I. New onset DM/uncontrolled DM/DM during acute illness
• At least FBG and one more pre-prandial value should be conducted every day.
• Glucose level must be checked whenever hypoglycemia is suspected.
II. Stable/well-controlled DM
• At least one test on alternate days at different times of the day, with at least
one FBG every week.
• Must check whenever hypoglycemia is suspected
.
• Based on the available resources and clinical judgment, the frequency of
glucose monitoring can be decided by the treating physician.
RSDDI recommendations on frequency of SMBG

19. Recommended care and limited care recommendations by RSSDI experts for frequency/timing of SMBG .
Monitoring
techniques
Recommended care for different conditions Limited care for different conditions
SMBG
4. Diabetes in pregnancy
I. Patients on OADs or insulin
• Monitoring should be carried out at least 4 times/day (FBG and
3 post-prandial values).
• Based on the available resources and clinical judgment, the
frequency of glucose monitoring can be decided by the treating
physician.
II. Patients on lifestyle modifications
• A day profile once a week, which should include FBG and 3 post-
prandial values at least once a week or staggered over a week.
• Based on the available resources and clinical judgment, the
frequency of glucose monitoring can be decided by the treating
physician.
• Based on the available resources and clinical judgment, the
frequency of glucose monitoring can be decided by the treating
physician.
4. Diabetes in pregnancy
I. Patients on OADs or insulin.
• Paired testing to be performed every day (pre- and post-breakfast on 1st day,
pre- and post-lunch on 2nd day, pre- and post-dinner on 3rd day, and then
keep repeating the cycle).
• Based on the available resources and clinical judgment, the frequency of
glucose monitoring can be decided by the treating physician.
II. Patients on lifestyle modifications.
• One FBG and one post-prandial value every week (any meal, preferably largest
meal of the day).
• Based on the available resources and clinical judgment, the frequency of
glucose monitoring can be decided by the treating physician.
RSDDI recommendations on frequency of SMBG
Recommended care: is defined as evidence-based care that is cost-effective. Limited care: is defined as the lowest level of care that aims to achieve the major objectives of diabetes management provided in healthcare settings with very limited
resources such as drugs, personnel, technologies, and procedures.

20. Blood Glucose Monitoring(BGM) Continuous Glucose Monitoring (CGM)
• Patients monitoring may be
infrequent or intermittent
• their reports may be inaccurate
• Overnight glucose levels are seldom
measured
• can miss out on true
hypoglycemia/hyperglycemia events
• higher patients acceptance
• more frequent information
• greater proportion of patients to
achieve target glucose and A1C levels
• expense
• calibration of devices
• comfort/ convenience and patient
acceptance
• better option for insulin patients
Method of GM did not affect patient quality of life, A1C was lowered by 0.3% in
patients with CGM compared to BGM

21. Continuous glucose monitoring (CGM)
3
• CGM is a simple, minimally invasive technique in which a sensor is inserted subcutaneously that
automatically measures glucose concentrations from the interstitial fluid of the patient and helps to
understand dynamic changes in glucose levels.
• Based on the device characteristics, there are real-time CGM (rt-CGM), and intermittently scanned
CGM (isCGM).
CGM advantages
• The recorder receives a signal every few seconds, and then converts the average recorded signal
into a glucose level every 1-5 min and saves it. This level can vary depending on the type of sensor.
Patients need to wear the sensor for 7-14 days based on the type of CGM used.
• CGM technology provides an ambulatory glucose profile (AGP) of the glycemic pattern, which
can be evaluated for formulating treatment modalities or dose adjustments for the patients.
• Based on the usage, CGM is further classified as personal CGM and professional CGM.

22. Continuous glucose monitoring (CGM)
• Evaluating daily blood glucose variations and identifying hyperglycemic and hypoglycemic events, especially
nocturnal hypoglycemia is feasible with CGM system
• CGM is particularly beneficial for patients with T1D and T2D (receiving insulin therapy) with poor glycemic
control and can be used along with SMBG for detecting hypoglycemia.
• CGM can evaluate intra- and inter-day blood glycemic variability and facilitates more frequent monitoring.
• The glucose pattern created by CGM helps patients understand the effect of lifestyle modification and
medication adherence in reducing GV, thereby facilitating better management of diabetes in insulin-treated
patients.
• CGM data is beneficial for clinicians to distinguish between hyperglycemia and rebound from hypoglycemia
CGM advantages

23. Time-in-range (TIR)
3
• The TIR is considered an innovative metric of CGM for assessing glycemic control in patients with T1D
and T2D. TIR is the percentage of time the glucose level is within the preferred glycemic range.
• Reduced TIR can be a predictor of microvascular complications.
• Time-above-range (TAR) and time-below-range (TBR) can help in assessing treatment efficacy.
• A higher level of TIR is associated with a lower level of HbA1c.

25. Oral Glucose tolerance test
Indications :
1.Diagnosis of Type 2 Diabetes Mellitus:
1. When fasting glucose levels or Hemoglobin A1c (HbA1c) are inconclusive or
borderline.
2. Especially useful in situations where there are symptoms of diabetes but fasting
glucose levels are not diagnostic.
3. Post transplant
2.Diagnosis of Gestational Diabetes:
1. Routinely performed between 24 and 28 weeks of pregnancy to screen for
gestational diabetes.
2. May be done earlier in pregnancy if the woman is considered high-risk.
3. Maybe needed post pregnancy to identify woman at risk for overt diabetes
3.Diagnosis of Prediabetes:
1. To identify individuals with impaired glucose tolerance, which is an intermediate
stage between normal glucose metabolism and diabetes.
4.Evaluating Patients with Symptoms of Hypoglycemia:
1. Used to diagnose postprandial or reactive hypoglycemia.
2. Helps to determine how the body is managing glucose.
5.Assessment of Patients with Polycystic Ovary Syndrome (PCOS):
1. PCOS is often associated with insulin resistance, and an OGTT can help evaluate
this aspect.
2. Helps in tailoring treatment strategies, especially in those trying to conceive.
6.In Cases of Unexplained Weight Loss or Fatigue:
1. When these symptoms are suggestive of an underlying metabolic disorder.
7.In Research Settings:
1. Used in clinical studies and research to understand glucose metabolism in various
conditions or in response to certain treatments.
8.After Bariatric Surgery:
1. To assess glucose tolerance and the effectiveness of the surgery in patients with
obesity and diabetes.

27. Advances in Diagnosis - C Peptide Assay
• The C-peptide assay is a useful test for identifying
the type of diabetes as well as in predicting the
response to therapy
• C-peptide test may be used to
• Find cause of hypoglycemia
• Manage diabetes treatment
• Monitor treatment
• To distinguish between T1D and T2D

28. Interpretation of C-Peptide results

29. Special Tests for Classification of DM
Pippitt K et al. Am Fam Physician. 2016 Jan 15;93(2):103-109

30. Gestational Diabetes (GDM) – PAPP-A2 Biomarker
• PAPP-A2 - pre-screening biomarkers for gestational diabetes
• Other biomarkers to detect GDM –
• soluble tumour necrosis factor-like weak inducer of apoptosis
(sTWEAK) – levels decrease in women with early GDM
• Relaxin-2 : Higher levels at 12 weeks of pregnancy complicated with
GSM
The pre-screening blood test would eliminate the burden and cost of having
to perform OGTTs in women at low risk of gestational diabetes
Pregnancy-Associated Plasma Protein-A2 (PAPP-A2) is a protease that cleaves
insulin-like growth factor-binding protein (IGFBP)
Alonso Lopez Y, et al., (2017). Plasma levels of relaxin-2 are higher and correlated to
C-peptide levels in early gestational diabetes mellitus. Endocrine, 57(3), 545–547.

31. Diabetes in the Young
Type 1 Diabetes

32. Algorithm for
differential
diagnosis of
diabetes in youth
Unnikrishnan R, Shah VN, Mohan V. Challenges in diagnosis and management of
diabetes in the young. Clin Diabetes Endocrinol. 2016

34. T1D disease progression
Starting point
Genetic risk
The road to T1D starts here
• All people with type 1 diabetes have
the genes associated with type 1
diabetes.
• The risk in the general population is 1
in 300
• Family members have a 15 times
higher risk of developing T1D
• The relative risk is 1 in 20
1
20

36. Autoantibodies in Type 1 Diabetes
➢ 4 autoantibodies are markers of beta cell autoimmunity in type 1 diabetes: islet cell antibodies (ICA,
against cytoplasmic proteins in the beta cell), antibodies to glutamic acid decarboxylase (GAD-65), insulin
autoantibodies (IAA), and IA-2A, to protein tyrosine phosphatase.
➢ Autoantibodies against GAD 65 are found in 80% of patients with type 1 diabetes at clinical presentation.
➢ Presence of ICA and IA-2A at diagnosis for type 1 diabetes range from 69-90% and 54-75%, respectively.
➢ IAA prevalence correlates inversely with age at onset of diabetes; it is usually the first marker in young
children at risk for diabetes and found in approximately 70% of young children at time of diagnosis.
➢ In the Diabetes Autoantibody Standardization Program 2000 workshop, the ELISA for the insulin
autoantibody (IAA) assay ranged in sensitivity of 4-42%; the standardization of the insulin antibody assay
continues to be more challenging than for GAD or IA-2A antibodies.

37. Staging of T1DM
Stage 1 Stage 2 Stage 3
Characteristics
• Autoimmunity • Autoimmunity • Autoimmunity
• Normoglycemia • Dysglycemia • Overt hyperglycemia
• Presymptomatic • Presymptomatic • Symptomatic
Diagnostic criteria
• Multiple islet
autoantibodies
• No IGT or IFG
• Islet autoantibodies
(usually multiple)
• Dysglycemia: IFG and/or
IGT
• FPG 100–125 mg/dL
(5.6–6.9 mmol/L)
• 2-h PG 140–199 mg/dL
(7.8–11.0 mmol/L)
• A1C 5.7–6.4% (39–47
mmol/mol) or ≥10%
increase in A1C
• Autoantibodies may
become absent
• Diabetes by standard
criteria
FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; 2-h PG, 2-h plasma glucose

38. Glycemic targets for Type 1 diabetes

39. Screening recommendations
for Vascular Complications

40. Risk-based screening for type 2 diabetes or prediabetes in
asymptomatic children and adolescents in a clinical setting
Diabetes Care Volume 46, Supplement 1, January 2023
Maternal history of diabetes or GDM
during the child’s gestation A
Family history of type 2 diabetes in
first- or second-degree relative A
Race/ethnicity (Native American,
African American, Latino, Asian
American, Pacific Islander) A
Signs of insulin resistance or conditions associated
with insulin resistance (acanthosis nigricans,
hypertension, dyslipidemia, polycystic ovary syndrome, or
small-for-gestational-age birth weight) B
Testing should be considered in youth*
who have overweight (≥85th percentile) or
obesity ≥95th percentile)
GDM, gestational diabetes mellitus.
*After the onset of puberty or after 10 years of age, whichever occurs earlier. If tests are normal, repeat
testing at a minimum of 3-year intervals (or more frequently if BMI is increasing or risk factor profile
deteriorating) is recommended. Reports of type 2 diabetes before age 10 years exist, and this can be
considered with numerous risk factors.
one or more additional risk factors based
on the strength of their association with
diabetes
OR

41. ❑ Asymptomatic Children: –
• Overweight: –
• BMI > 85th percentile for age
and sex
• Weight for height > 85th
percentile
• Weight > 120% of ideal for
height
❑ Any two of the following risk factors:
✓ Family history of T2DM
✓ Race/Ethnicity
✓ Signs of Insulin resistance or
associated conditions
✓ Maternal history of Diabetes or GDM
Testing Protocol in T2DM (< 18yrs)

42. Monogenic Diabetes

43. GENETICS OF MODY
Type Gene Locus Clinical features
MODY 1 HNF4A 20q12-q13.1 Mild-severe fasting and postprandial plasma glucose (PG) Respond well to sulphonylurea
agents
MODY 2 GCK 7p15-p13 Mild fasting hyperglycaemia. Less than 50 percent of carriers have overt DM, and
microvascular complications of diabetes are rare.
MODY 3 HNF1A 12q24.2 Same as MODY 1
MODY 4 IPF1/ PDX1 13q12.1 Pancreatic agenesis.
MODY 5 HNF1B 17cen-q21.3 Overt DM in association with renal and genito urinary abnormalities.
MODY 6 NEUROD1 2q32 Rare, with phenotype characterized by obesity and insulin resistance.
MODY 7 KLF11 2p25 Very rare; phenotype ranges from impaired glucose tolerance or impaired fasting glucose
to overt DM.
MODY 8 CEL 9q34.3 Very rare; associated with both exocrine and endocrine pancreatic deficiency and with
demyelinating peripheral neuropathy.
MODY 9 PAX4 7q32 Very rare. Crucial transcription factor for beta cells development
MODY 10 INS 11p15.5 Very rare. Usually associated with neonatal diabetes. Rare < 1% cases.
MODY 11 BLK 8p23-p22 These adapter proteins nucleate formation contributes to the qualitative and quantitative
control of B-cell signaling.
MODY 12 ABCC8 11p15.1 Very rare. Usually associated with neonatal diabetes. Rare < 1% cases.
MODY 13 KCNJ11 11p15.1 Very rare. Usually associated with neonatal diabetes. Rare < 1% cases.

44. Monogenic Diabetes Type 1 Diabetes
Three Generation transmission with
only one parent affected
Family History usually negative
C-Peptide Preserved C-Peptide Absent
Pancreatic Autoantibodies absent Pancreatic Autoantibodies maybe
present
Responds to Suphonylureas Needs lifelong insulin therapy
Differences between Monogenic Diabetes (HNF1⍺ and HNF 4⍺ mutations)
and Type 1 Diabetes

45. Differences between Monogenic Diabetes (HNF1⍺ and HNF 4⍺ mutations)
and Early Onset Type 2 Diabetes
Monogenic Diabetes Early Onset Type 2 Diabetes
Non-Obese Obese/Overweight
Acanthosis nigricans uncommon Acanthosis common
Three generation transmission with only
one parent affected
Both the parents could be affected
Only insulin secretory defect Defect in insulin secretion and insulin
resistance
Seen in all populations Usually in population with high
prevalence of T2DM
Responds better to Sulphonylureas Responds better to Metformin

46. Type 2 Diabetes

47. 48
Pima Indians
Egyptians
NHANES III
Prevalence of retinopathy by deciles of the distribution of FPG, 2HPG, and A1C
Advantages of A1C testing compared with FPG or 2HPG for the diagnosis of diabetes
● Standardized and aligned to the DCCT/ UKPDS; measurement of glucose
is less well standardized
● Better index of overall glycemic exposure and risk for long-term
complications
● Substantially less biologic variability
● Substantially less preanalytic instability
● No need for fasting or timed samples
● Relatively unaffected by acute (e.g., stress or illness related)
perturbations in glucose levels
● Currently used to guide management and adjust therapy
The International Expert Committee DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009

48. 49
D. Tsilingiris, N.G. Vallianou and M. Dalamaga Metabolism Open 10 (2021) 100091

49. Criteria for diagnosis of diabetes
01 FPG ≥126 mg/dL
02
03
04
2-h PG ≥200 mg/dL during OGTT.
A1C ≥6.5%
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma
glucose ≥200 mg/dL.
OR
OR
OR
DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; NGSP, National Glycohemoglobin
Standardization Program; WHO, World Health Organization; 2-h PG, 2-h plasma glucose.
*In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples

50. Gestational Diabetes

51. Gestational Diabetes
• GDM – Most common during second and third
trimester
• High risk group –
• Old age
• Overweight/obese/BMI greater than 30
• Excessive weight gain during previous pregnancy
• Family history
• h/o PCOs
• Large baby in previous pregnancy
• Presence of signs of insulin resistance viz. acanthosis
nigricans
• Complication include –
• foetal macrosomia
• Preeclampsia
• polyhydramnios
The pre-screening blood test would eliminate the burden and
cost of having to perform OGTTs in women at low risk
of gestational diabetes
Alonso Lopez Y, et al., (2017). Plasma levels of relaxin-2 are higher and correlated to C-
peptide levels in early gestational diabetes mellitus. Endocrine, 57(3), 545–547.

52. Screening for and diagnosis of GDM
Diabetes Care Volume 39, Supplement 1, January 2016
Recommendations
• Test for undiagnosed type 2 diabetes at the first prenatal visit in
those with risk factors, using standard diagnostic criteria. (B)
• Test for gestational diabetes mellitus at 24–28 weeks of gestation
in pregnant women not previously known to have diabetes. (A)
• Screen women with gestational diabetes mellitus for persistent
diabetes at 6–12 weeks postpartum, using the oral glucose
Tolerance test and clinically appropriate nonpregnancy
diagnostic criteria. (E)
• Women with a history of gestational diabetes mellitus should
have lifelong screening for the development of diabetes or
prediabetes at least every 3 years. (B)
• Women with a history of gestational diabetes mellitus found to
have prediabetes should receive lifestyle interventions or metformin
to prevent diabetes. (A)

53. Various diagnostic criteria for gestational diabetes
mellitus and cut-off values
World J Diabetes 2017 December 15; 8(12): 489-506

54. DIPSI Guidelines for screening of GDM in early pregnancy
DIPSI Guidelines, J Assoc Physicians India, 2006
Screen all pregnant women
South Asians – At high risk ethnic group for
development of diabetes
Hence in India, all pregnant women of high risk
ethnic group needed to be screened for GDM

55. Prediabetes

56. 57
Current Diagnostic Criteria for Prediabetes
Prevalence of prediabetes in US adults aged 20 or older
according to clinical definitions of prediabetes.
Hazard ratios (95% confidence intervals) for the associations of different definitions of
prediabetes with incident diabetes, chronic kidney disease, cardiovascular disease, and
all-cause mortality in the community-based ARIC study
Annu. Rev. Public Health 2021. 42:59–77

57. Incidence of Diabetes (WHO Criteria) for Combinations of IFG and IGT
(WHO Criteria) for Combinations of IFG and IGT
FPG/2hPG Incidence OR
(mg/dl) (%) (95% CI)
Normal <110/140 4.5 1.0
IFG and NGT 110-126/<140 33 10.0
NFG and IGT <110/140-200 33.8 10.9
IFG and IGT 110-126/140-200 64.5 39.5
Hoorn Study, Follow-up 5-6 year
De Vegt et al, JAMA 285:2109-13, 2001
US: Randomized clinical trials reported annual rates of progression from prediabetes to
diabetes that ranged from 5.8% to 18.3%

58. 59
Pharmaceutical trials for diabetes prevention
Annu. Rev. Public Health 2021. 42:59–77

59. Prediabetes: Screening, Diagnosis, Early Intervention
• Screen for diabetes in overweight or
obese adults (BMI >25 kg/m2) with
one or more risk factors at any age.
• Screen asymptomatic adults from
the age of 35 (instead of 45 years)
• Diagnostic tests:
• fasting glucose
• glucose tolerance curve
• HbA1c
ADA Standards of Care.
Diabetes Care Suppl 1, 2013
Consider intensive preventive
approaches in people at high risk
of progression to diabetes:
•BMI >35 kg/m2
•Fasting plasma glucose levels of
110 to 125 mg/dL
•2-h glucose tolerance curve:
173 to 199 mg/dL
•A1C > 6.0%
•History of gestational diabetes
mellitus

60. Latent Autoimmune Diabetes in Adults (LADA)

61. Broad characteristics of LADA
• Age .30 years
• Family/personal history of autoimmunity
• Reduced frequency of metabolic syndrome compared with T2D—lower HOMA, lower
BMI, lower blood pressure, and normal HDL compared with T2D
• No disease-specific difference in cardiovascular outcomes between these patients
and those with T2D
• C-peptide levels decrease more slowly than in T1D
• Positivity for GADA as the most sensitive marker; other autoantibodies less frequent
(ICA, IA-2A, ZnT8A, and tetraspanin 7 autoantibodies)
• Non–insulin requiring at onset of diabetes. But will require insulin treatment much
earlier in the course of disease than Type 2 Diabetes

62. Fibrocalculous Pancreatic Disease (FCPD)

63. Criteria for diagnosis of Fibrocalculous pancreatic diabetes
(FCPD)
Diagnostic criteria for FCPD (Mohan et al.)
Patient should be from a tropical country
Diabetes should be present
Evidence of chronic pancreatitis must be present (abnormal pancreatic
morphology on sonography or CT scan, recurrent abdominal pain since
childhood, steatorrhea, abnormal pancreatic function tests)
Absence of other causes of chronic pancreatitis (alcoholism, hepatobiliary
disease, etc.)
Unnikrishnan R, Shah VN, Mohan V. Challenges in diagnosis and management of
diabetes in the young. Clin Diabetes Endocrinol. 2016
1
2
3
4

64. Usual Presentation

65. Glycemic Targets

66. Questions to Address
• What should the A1C be for most people & why?
• Who should we be more aggressive with & why?
• Who should we be less aggressive with & why?

67. Targets Checklist
✓ A1C ≤7.0% for MOST people with diabetes
✓ A1C ≤6.5% for SOME people with T2DM
✓ A1C 7.1-8.5% in people with specific features

70. Current A1C
<7%
Multiple
comorbidities
or
medications
that may
cause
hypoglycemia
Liberalize
Goal
Few
comorbidities
and
medications
unlikely to
cause
hypoglycemia
At Goal with
Caution
(continually
assess for
hypoglycemia)
7–8%
Medications
likely to
cause
hypoglycemia
Carefully assess for
hypoglycemia or
glucose excursions
Liberalize
Goal
At Goal
Present Not Present
Medications
unlikely to
cause
hypoglycemia
At Goal
> 8%
• Multiple comorbidities
• Limited life expectancy
• Difficulty coping
At Goal
Aim for
Goal
< 8%
Present Not Present
Goal-Setting Algorithm in the Elderly

71. Importance of good control of diabetes

72. Impact of bad glycemic legacy
Del Prato S. Diabetologia 2009; 52:1219–1226.
Time since diagnosis (years)
HbA
1c
(%)
1 2 3 8 9 12 13
6
4 5 10 11 14 15
7 16 17
9.0
8.5
8.0
7.5
7.0
6.5
6.0
9.5 Drives risk of
complications
Before entering VADT intensive treatment arm After entering VADT intensive
treatment arm
Generation of a
‘bad glycemic
legacy’

73. Diabetes control
during the 1st year
after diagnosis
future risk for diabetic
complications and
mortality
Neda Laiteerapong et al., Legacy Effect in Type 2 Diabetes: Cohort Study,
Diabetes Care Volume 42, March 2019
Strong
Association
Effects of Delay in treatment exposure
by 0-1 year in different HbA1c groups
HbA1c ≥6.5% increased microvascular and
macrovascular events
HbA1c ≥7.0% increased mortality
HbA1c ≥8.0% increasing microvascular
event and mortality risk

74. Glycemic control: how intensive?
Early and durable
• To avoid a vascular legacy of ‘hyperglycemic memory’
Intensive enough, but safely
• To minimize complications without causing hypoglycemic events
• And to be practicable without undue imposition
Integrated
• Within a comprehensive program to reduce cardiovascular risk

75. Key Messages

76. 1. Different societies have established diagnostic criteria of types of diabetes. We need to
We need to use this information to classify an individual patient.
2. There will always be ethnic variations which we have little information as of now till better
data exists through epidemiological studies
3. It is important to screen individual patients for diabetes based on their risk profiles. This will
help to optimize resources. In a country like India, where incidence is high, screening for diabetes
should have a low threshold
4. Institution of treatment to reach target goals early should be aggressively pursued to prevent
long term complications
5. Given the treatment modalities we have no patient should stay uncontrolled

77. Thank you