XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Classification and diagnosis of diabetes

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Hyperglycemia and Adverse Pregnancy Outcomes

Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome. In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action. More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes.

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The mechanisms of action of metformin

Background: There is no published literature on the profile of patients with tall stature (TS) from India. This study aimed to evaluate the etiological and clinical profile of patients with TS referred to our hospital. Materials and Methods: We performed a retrospective review of records of patients referred to us for evaluation of TS (January 2007 to March 2020). Relevant clinical, anthropometric, biochemical, and radiological data at presentation were recorded, and the final diagnosis reviewed. Results: The study included 16 subjects (6 boys, 10 girls) with a mean age at presentation of 13.2 ± 3.6 years. Most subjects were pubertal (n = 10) and belonged to the overweight or obese category (n = 10). The mean height and height standard deviation score (SDS) were 172.3 ± 20.3 cm and 3.6 ± 1.5, respectively, while mean mid-parental height (MPH) and MPH SDS were 168.8 ± 8.8 cm and 1.2 ± 0.9, respectively. The etiological diagnoses were familial TS (n = 9), acrogigantism (n = 3), obesity-related TS (n = 2), constitutional advancement of growth (n = 1), and Marfan syndrome (n = 1). The mean height SDS in subjects with acrogigantism was 6.4 ± 1.2 compared to 3.0 ± 0.6 in those with other etiologies of TS. Only one girl with familial TS and significantly increased predicted adult height (+4.56 SDS) opted for sex steroid therapy. Conclusion: Familial TS is the most common diagnosis among patients referred for evaluation to our hospital. One should consider the possibility of acrogigantism in patients with growth acceleration, extreme TS, and markedly increased gap between height SDS and MPH SDS. Most patients with familial TS require reassurance and sex steroid therapy should be reserved for highly selected cases.

Etiology and clinical profile of patients with tall stature: A single-center experience

A variety of injectable therapies are now available for use in patients of type 2 diabetes mellitus, when metformin alone proves inadequate. These injectable therapies include basal insulins, glucagon-like peptide 1 receptor agonists (GLP1RA), co-formulations of basal insulin with GLP1RA, and premixed or co-formulated dual action insulins. This article helps choose appropriate first injectable therapy in a rational manner, and achieve glycaemic control in an efficient way. The discussion utilizes the pharmacokinetic and pharmacodynamic properties of various injectable drugs to match them with various clinical situations. It highlights a gluco-phenotypic approach, utilizing readily available anthropometric measurements, glycaemic patterns, and other bio psychosocial parameters, to create a simple model which facilitates correct choice of first injectable therapy in type 2 diabetes.

Choice of first injectable therapy in type 2 diabetes.


 
 
 Intracerebroventricular streptozotocin injection at 3mg/kg of b/w causes phenotypes similar to that of sporadic Alzheimer’s disease (sAD) from 14th day post-injection. On the other hand, the body of evidence indicated that impairment in the sAD is the major contributor for cognitive decline. Taken together, we tested the adult neurogenesis hypothesis in streptozotocin model of sAD in female Wistar rats after extremely low magnetic stimulation (MF: 17.96, 50Hz, 2hr/day, 21days).
 
 
 
 33 rats were randomly divided into three groups viz. Sham+MF, AD and AD+MF. Consequently, animals were first induced AD with stereotaxic manipulation and then they were exposed to low frequency magnetic field stimulation, followed by terminal cognitive behavioural tasks brain tissue being isolated for both biochemical and subcellular expression experiments (ethical no. 12/IAEC-1/2017).
 
 
 
 Showed reduction in latency to the goal quadrant (p= 0.002) and transfer latency (p= 0.045) in AD+MF group versus AD. Even, Dirichlet distribution of time spent in 4 quadrants indicated un-uniform in all the groups except AD group (p= 0.067, LRS= 7.35). Further, cell count in CA3 and DG exhibited increase in cell density in AD+MF group (p<0.05). However, we found significant reduction in SOD1 activity after MF treatment (p= 0.035) but no change in GSH level in hippocampus and frontal cortex. Interestingly, these changes in AD+MF animals are associated with increase in density of BrdU+/Nestin+ cells in granular layer (p= 0.002) and hilus region (p= 0.0005) of DG along with increase in expression of L-type Ca2+ channels as compared to AD group.
 
 
 
 This experimental evidence suggests that non-invasive brain stimulation can promote adult neurogenesis by activating L-type ca2+ channels in the hilus, which intern helps in retention of long-term memory even after sAD.


1145 rtms treatment improved cognitive dysfunction through adult neurogenesis in icv-stz rat model of sporadic alzheimer's disease


 
 
 Intracerebroventricular streptozotocin (ICV-STZ) injection is among the best animal models to simulate sporadic Alzheimer’s disease (sAD). Abnormality in brain insulin signalling, neurodegeneration, neuroinflammation, cholinergic damage, mitochondrial dysfunction, genetic abnormality, respiratory problem, oxidative stress, gliosis, sleep disturbances are associated with cognitive abnormalities seen in ICV-STZ injected rats. Available experimental evidence has used varying doses of STZ (<1 to 3mg/kg) and studied its effect for different study durations, ranging from 14-21 (short), 30-42 (mild), 90-105 (moderate) and 250-270 (long) days. These studies indicated that 3mg/kg of body-weight is the optimum dose for inducing sAD in the rodents. However, studies on the pathological process with related the morphological and functional abnormalities reported were illusive.
 
 
 
 Hence in the present study, we have investigated the morpho-functional changes after 3mg/kg ICV-STZ treatment with a follow-up of two months in 54 male Wistar rats (ethical no. 937/IAEC/PhD-2016).
 
 
 
 Exhibited a spatial, episodic and avoidance memory decline and increase in anxiety (p<0.05) in ICV-STZ group progressively with time from 15th day to 60th day post-injection. Morphometry showed hippocampal atrophy with CA1, CA3 layer thinning (p ≤0.01) and loss of neurons (p<0.0001) associated with third ventricular enlargement (p= 0.007) in ICV-STZ rats versus sham, along-with extracellular amyloid plaque in AD rats with Congored staining. In addition, spine morphometry with Golgi-Cox impregnation of mossy fibre showed a reduction of spine density in AD group versus control and sham group (p<0.0001). Finally, immunohistochemistry of GSK3ß, PI3K and mtCOX-1 antigen in coronal sections revealed an increase in mean intensity of GSK3ß and decrease in PI3K and mtCox-1 in brain areas associated with limbic system in ICV-STZ group on 60th day.
 
 
 
 These findings suggest progressive dementia and anxiety in 3mg/kg STZ treated rats, which may be due to hippocampal atrophy, amyloidopathy, ventricular enlargement, synaptic dysfunction and deficits in energy homeostasis of brain.


1147 morpho-functional evaluation of 3mg/kg icv-stz rat showed sporadic alzheimer's like pathology with progressive dementia

Despite consensus on universal screening of women at 24-28 weeks for a diagnosis of gestational diabetes, controversy remains on an appropriate criterion. The study is aimed to find out the sensitivity and specificity of Diabetes in Pregnancy Study Group India (DIPSI) criteria compared to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosis of Gestational Diabetes Mellitus (GDM). A meta-analysis of studies comparing DIPSI as an index test to IADPSG as the reference test for diagnosing GDM was carried out. A total of 8 comparative studies were included. Pooled analysis showed a sensitivity of 0.44 [0.29 to 0.60] and specificity of 0.97 [0.94 to 0.98], which means the index test DIPSI will correctly identify only 44% of the subjects who have the disease (GDM positive) but it will also fail to identify 56% of the GDM positive subjects. Derek's funnel graph revealed fewerchances of publication bias. Though convenient, DIPSI criteria was not found to be sensitive enough for a diagnosis of GDM and missed an opportunity to improve pregnancy and subsequent long-term outcomes for a substantial number of women. Further studies should focus on comparing pregnancy outcomes for the two criteria, so that decision to adopt any criteria is more evidence-based. 

Meta-analysis comparing diabetes in pregnancy study group India (DIPSI) vs the international association of the diabetes and pregnancy study groups (IADPSG) criteria for diagnosis of gestational diabetes among Indian population.

Yashdeep Gupta

Papers

Etiology and clinical profile of patients with tall stature: A single-center experience

Choice of first injectable therapy in type 2 diabetes.

1145 rtms treatment improved cognitive dysfunction through adult neurogenesis in icv-stz rat model of sporadic alzheimer's disease

1147 morpho-functional evaluation of 3mg/kg icv-stz rat showed sporadic alzheimer's like pathology with progressive dementia

Meta-analysis comparing diabetes in pregnancy study group India (DIPSI) vs the international association of the diabetes and pregnancy study groups (IADPSG) criteria for diagnosis of gestational diabetes among Indian population.