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HCFI Dr KK Aggarwal Research Fund 20 April 2025
Minutes of an International Weekly Meeting held by HCFI Dr KK Aggarwal Research Fund
Topic: Diabetes in Women: Do we require gender-specific guidelines?
Speaker: Dr. Shalini Jaggi, Dip Diab (UK), Dip Endo (UK), F Diab, FRCP (London, Edin, Glasg), FACE (USA), Consultant Diabetologist & Director, Lifecare Diabetes Centre, New Delhi, Chair Elect, RSSDI-Delhi Chapter, Member, Governing Council, DIPSI
March 8, 2025, Saturday
9.30-10.30am
· Global guidelines on diabetes management do not really take gender into perspective when it comes to prescribing treatment.
· The experience of diabetes itself is different in women; lifecycle of women is different; diabetes has more serious adverse outcomes in women; the socioeconomic, cultural and other social determinants; there are gaps in gender-specific health research and technology.
· It's time to address the gender inequities that occur in healthcare, especially in the Southeast Asian subcontinent, view therapeutics with the gender lens and prioritize gender mainstreaming and benefits to actually reach out to half of the world's population with diabetes.
· In 2021, there were 17 million more men with diabetes compared to women but the gap seems to be fast closing and is expected to be 14 million by 2030 and 11 million by 2045.
· More women are dying of diabetes or diabetes-related complications once they are in the postmenopausal age group compared to men.
· The ICMR-INDIAB 17 study projections for metabolic disease prevalence in India show that diabetes, prediabetes, dysglycemia, hypertension, obesity especially abdominal obesity, hypercholesterolemia, high LDL cholesterol are definitely rising and are already very high.
· More women have prediabetes than men; women present more with IGT compared to men who present with IFG.
· A study from a private tertiary Diabetes Care Center in South India has demonstrated sex based differences in clinical profile and complications amongst individuals with type 2 diabetes. Women had higher BMIs than men. More females than males were sedentary (58.7% vs 48.0%). Only 12.9% of females performed the recommended >150 minutes/week of physical activity vs 24.9% of males. Obesity, hypothyroidism and cancer were more common in females than in males. Males had higher FPG, PPPG, HbA1c, serum cholesterol, HDL-cholesterol and LDL-cholesterol than females. However, after the age of 44 years, control of diabetes was worse among females.Only 18.8% of the females achieved glycemic control (HbA1c < 7%) compared to 19.9% in males.
· Biological sex causes sex differences through genetic and hormonal influences affecting disease pathophysiology, clinical manifestations and even response to treatment. Sex also influences behaviors. Gender-related behavior such as smoking, lifestyle, nutritional habits, perceived stress, modulate expression of biological sex.
· Drivers of diabetes in women include healthcare disparities, financial dependence, obesity sedentary lifestyle, pregnancy, GDM, PCOS, menopause, low birth weight, stress.
· There are sex dimorphisms in body composition, there are some inherent biological differences in cardiometabolic pathways, gender differences in attitudes and perception of the patient, social determinants of health and healthcare based inequities and biases.
· There are also some physiological sex differences. Men have less subcutaneous fat and more visceral fat. Women have less visceral fat but they also have less muscle mass.
· Women seem to be metabolically healthy obese, but this is transient and most eventually progress to pathological obesity resulting in a plethora of metabolic disorders.
· The different stages of life cycle of a women have a different plethora of hormonal disbalance, which must be addressed when managing women with diabetes.
· There is a direct link between maternal health and NCDs in the offspring.
· Birth weight is a very important predictor for development of type 2 diabetes.
· The cycle of diabetes continues from the mother to the daughter and to the next generation - the transgenerational risk.
· The origin of adult disease is in this fetal programming. Maternal nutritional imbalance and metabolic disturbances have a persistent and intergenerational effect on the health of offspring and risk of diseases such as obesity, diabetes and CVD.
· Prenatal development is a critical period in the etiology of human diseases, especially when unfavorable environment interacts with a genetic predisposition.
· PCOS in adolescence is very common endocrine disorder affecting about 5-10% of the female population. It is a complex metabolic disease with insulin resistance as the central factor in pathophysiology. IR is linked to diabetes, hypertension, dyslipidemia, central obesity, hyperandrogenism, reproductive dysfunction, malignancies and macrovascular complications.
· The onset of prediabetes in adolescents is on a rise due to sedentary lifestyle, improper eating habits, increased stress levels and increased screen time.
· A positive family history, lack of exercise and the hormonal changes in puberty push the adolescent girls towards an impaired glucose metabolism.
· Women with PCOS have a higher prevalence of metabolic syndrome. Insulin resistance plays a major role in both. Hyperandrogenism is linked to several components of metabolic syndrome. There is more visceral fat, decreased lipolysis, insulin sensitivity, HDL-cholesterol and increased LDL-cholesterol.
· Insulin resistance is a precursor to diabetes. Women with PCOS have higher incidence of IGT/T2DM.
· Oligomenorrhea, a surrogate marker for PCOS, that alone predicts 2-2.5 fold increased risk of type 2 diabetes especially in females who have a family history of diabetes.
· If measures are not taken early, 35% of patients with PCOS will have IGT and 10% develop Type 2 diabetes by 40 years of age.
· The conversion rate from IGT to diabetes is 5-10 times higher in women with PCOS.
· There is a need for unique strategies in young women with PCOS and type 2 diabetes: Lifestyle changes should be aimed at weight loss and metabolic well-being. Avoid the effects of hyperinsulinemia, lower the risk of metabolic syndrome, type 2 diabetes, cardiovascular disease, psychological support and emotional well-being is very important. Lower the risk for GDM and pharmacological management has to be as per the guidelines but it has to be gender sensitive.
· Men and women are not equal when it comes to heart disease. Cardiovascular disease amongst women is understudied, under-recognized, underdiagnosed, undertreated; also, women are often under-represented in clinical trials. 35% of all deaths in women worldwide are caused by cardiovascular disease.
· Symptoms like back, neck and jaw pain, nausea and vomiting in women are often attributed to non-cardiac causes, which often results in a delay of medical treatment. This has to change. Noninvasive testing has a lower predictive accuracy. There is a higher incidence of silent MI in women.
· Non-specific symptoms like unusual upper body discomfort, shortness of breath, unusual fatigue, sudden dizziness, nausea, breaking out in cold sweat in women are often ignored.
· Diabetes increases coronary heart disease risk by 4-6-folds in women with diabetes compared to only 2-3 folds in men with diabetes.
· The Nurses Health Study has shown that the relative risk of MI or stroke goes up as diabetes is diagnosed. Women lose their normal female protection from cardiovascular disease as menopause occurs. They had nearly 50% greater risk of CVD and 3-7 times more likely to develop or die of heart disease. Women are more likely to be disabled after a stroke.
· Women have more severe heart disease than men. The incidence of sudden deaths with no previous symptoms is 63% compared to 50% in men.
· Men present with reduced ejection fraction heart failure (HFrEF; weak heart muscle) whereas women are more likely to develop heart failure with preserved ejection fraction (HFpEF; stiff heart muscle).
· Diabetes in women is associated with an increased risk of stroke. Women with stroke appear to become more severely ill following a stroke. These sex differences have profound implications for effective prevention and treatment of stroke.
· For CVD, there is a need to acknowledge the sex-specific risk factors like menopause, gestational diabetes, hypertension in pregnancy, preterm delivery, PCOS. The impact of some underrecognized risk factors - socioeconomic deprivation, poor health literacy, environmental risk factors, abuse, psychosocial risk factors must also be acknowledged.
· It’s prudent to keep cardiovascular prevention in mind when managing women with diabetes. Avoid drugs that can cause CV harm. Prescribe drugs that offer cardioprotection.
· Undernutrition and overweight/obesity are both higher for women than men.
· The Western New York study showed that there are sex differences in endothelial function. The biomarkers of endothelial dysfunction (E-selectin, sICAM-1) and fibrinolysis (PAI-1) are increased in women who develop prediabetes compared to the controls.
· Abdominal visceral adipose tissue is more strongly associated with insulin resistance in women than in men. Obesity and metabolic dysfunction in women reduce the inherent sex hormone protection from cardiovascular disease.
· Women take longer time to develop type 2 diabetes so they remain in the dysglycemic prediabetic zone for a much longer time. They have a greater deterioration of cardiovascular risk factors than men. Women have a stronger association of abdominal visceral fat with insulin resistance.
· An unplanned pregnancy is a red flag for these women. A girl who gets diabetes at an early age needs to be counseled on the risks of an unplanned pregnancy, especially when glucose levels are not on target to have better maternal as well as neonatal outcomes.
· Patient education, physician-directed medical care, screening for complications, counselling - all these concepts of preconception care have to be woven into management.
· Safety of medicines before and during pregnancy is very important. In India, DCGI has recently approved metformin. It may be used if no contraindication or intolerance. A slightly increased risk of prematurity or small for gestational age has been seen in infants who were exposed to metformin in utero but largely metformin has been found to be safe. However, insulin remains gold standard; it is safe and well-tolerated. Review all concomitant medications. Stop ACEIs/ARBs, statins. Change over to the safer alternatives. Start low-dose aspirin at about 12-16 weeks of gestation to prevent pre-eclampsia.
· For lactating women, it is advisable to continue insulin till she stops feeding. Metformin is the only drug that is used in breastfeeding; all the other oral anti-diabetic medicines need to be stopped. Once they stop lactating it is advisable to transition to oral drugs if they have pre-existing type 2 diabetes.
· Weight gain at midlife with central distribution of fat leads to increase in insulin resistance and impacts glycemic control and CV health.
· Osteoporosis is very common; hence, bone health assessment is important.
· Antidiabetic agents conducive to weight loss or are weight neutral to be used and caution has to be exercised while using TZDs.
· The protection provided by estrogen against fatty liver disease is lost in menopause putting the woman at risk of NAFLD/MASLD.
· Diabetes should be managed with a multipronged approach in postmenopausal women. Special considerations for management include: dietary interventions, dietary supplements, physical activity, OHAs, insulin, glycemic control, HRT.
· The relative risk of fractures with glitazones is increased one-fold among men, whereas in women this risk increased 2.23 times. So abstain from prescribing glitazones among women.
· There are also gender differences in diabetes attitudes and adherences. Depression and anxiety are twice as common in women with diabetes compared to men with diabetes. Diabetes distress is also much higher in females.
· Very few women are actually self-reliant and are financially dependent for disease management.
· Type 2 diabetic women are not small type 2 diabetic men, says an article published in 2021; there are sex and gender differences in men and women respond to anti-diabetic drugs.
· The incidence of microvascular complications neuropathy, nephropathy, retinopathy much higher in women compared to men. Evaluation of such microvascular complications should be integrated into diabetes management in these women.
· Antidiabetic drug-associated adverse events are more frequently reported by women than men throughout body organs and drug classes, especially in GLP1-RA, SGLT2i and TZDs.
· Urinary tract and genital infections were all reported by women with SGLT2i, edema in TZAs and hyperglycemia in insulin users.
· Women face gender differences and barriers to accessing type 2 diabetes care such as lack of time due to caregiving role, giving less priority to their own health, lack of education, sociocultural barriers, lack of family and social support, health system barriers, failure to provide adequate health information, unsupportive nature of health professionals, lack of sensitization of health professionals towards these important factors.
· The percentage of high and very high therapeutic inertia, physician failure to begin or intensify indicated treatment, is significantly higher in women.
· Diabetes in women is different, it is difficult, it is disabling, often dismissed and is associated with more deaths.
· There is a need to evaluate if the current recommendations for diabetes management identify the need gaps and unique challenges for diabetes in women.
· We need to have strategies that are sensitive to woman's life cycle and the unique challenges and limitations that she faces at different stages of her life.
· All risk calculators must be revised based on all the evidence that has emerged. The recommendations need to be tweaked.
· If you have a woman in the reproductive age group and who is planning a pregnancy you need to follow the preconception pregestational diabetes guidelines. If there is no contraception and pregnancy desired?, recommend contraception and discuss preconception care.
· Avoid medications that maybe unsafe in pregnancy. Avoid medications that increase risk of fractures and cause bone loss especially in postmenopausal women. Avoid medications that increase the risk of UTI/GTI.
· It is time to recognize and accept the gender-specific differences and practice gender sensitive strategies to deliver quality care to all women with diabetes through different stages of their life course.
Participants
Dr Angelique Coetzee, South Africa
Dr Akhtar Hussain, South Africa
Dr Ashraf Nizami, Pakistan
Dr Qaisar Sajjad, Pakistan
Dr Prakash Budhathoki, Nepal
Invitees
Dr Mulazim Hussain Bukhari, Pakistan
Dr Poonam Saith
Dr B Kapoor
Dr Amlendu Yadav
Dr Noorul Anwar
Dr Kiran Vinayek
Dr Sanchita Sharma, Editor, IJCP Group
Moderator
Mr Saurabh Aggarwal
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