​Kembara Xta - Medicine - Diabetes Mellitus Type 1

​Kembara Xta - Medicine - Diabetes Mellitus Type 1 
Introduction Type 1 diabetes mellitus (T1DM) is a chronic condition brought on by a lack of insulin after -cell death.
Results in hyperglycemia and the possibility of end-organ problems
Ketosis or diabetic ketoacidosis (DKA), which typically develops quickly, absolute insulin reliance, polyphagia, polydipsia, polyuria, and nocturia
- Body habitus: at diagnosis, typically normal or slender physique
Endocrine, metabolic, cardiovascular, neurological, renal, and ophthalmic systems are affected

pregnant women's issues
T1DM increases the risk of pregnancy failure, spontaneous abortion, fetal abnormalities, preeclampsia, fetal death, macrosomia, neonatal hypoglycemia, and neonatal hyperbilirubinemia in both the mother and the fetus.
The significance of maintaining glycemic control as close to normal as is safely possible to lower congenital abnormalities should be covered in preconception counseling.
Fasting glucose levels should be less than 95 mg/dL, and 1- or 2-hour postprandial glucose levels should be less than 140 mg/dL.
Due to higher RBC turnover, glycated hemoglobin (HbA1c) is slightly lower during pregnancy. If hypoglycemia cannot be avoided, the HbA1c target should ideally be 6%; nevertheless, it might be modified to 7% in such cases.

Dilated eye exams should be performed before becoming pregnant or during the first trimester, followed by monitoring during each trimester and for a year after delivery.

If there are no contraindications, low-dose aspirin should be provided to women with T1DM by the end of the first trimester in order to reduce the risk of preeclampsia (typical dose is 81 mg/day).


Prevalence and incidence of disease 

Bimodal age of presentation ranges from 4 to 6 years old to 10 to 14 years old (early puberty).
Incidence
Incidence is 23.6/100,000 in non-Hispanic white children and adolescents in the United States; other racial and ethnic groups have lower rates.
Child Safety Considerations
T1DM symptoms in infants and toddlers can be imperceptible or pass for symptoms of another condition.
Prevalence
The incidence of type 1 diabetes in the United States ranges from 2.6/1000 to 3.7/1000.

Pathophysiology 
Diabetes that is immune-mediated and idiopathic are the two basic types of T1DM.
Diabetes that is immune-mediated results in the cellular-mediated autoimmune death of pancreatic cells (markers include autoantibodies to the tyrosine phosphatases IA-2 and IA-2, GAD65, and zinc transporter 8 autoantibody [ZnT8A]). To rule out MODY-monogenic diabetes, get three antibody tests (GAD65, IA-2A, and ZnT8).
Idiopathic diabetes has no recognized cause for its persistent insulinopenia; it is also prone to ketoacidosis without having any signs of autoimmunity.
In 85–90% of people, at least one autoantibody is present.

Genetics: HLA associations (HLA-DQA1, HLA-DQB1, and DLA-DRB1), with linkage to the DQA and DQB genes, and influence by the DRB genes. These antibodies may be protective or predisposing.
Although there are more than 40 loci, the main susceptibility locus maps to the HLA class II genes at 6p21 (accounting for 30–50% of hereditary T1DM).


perinatal factors (maternal age, history of preeclampsia, neonatal jaundice), viral infections, vitamin D insufficiency, high birth weight for gestational age, and lower gestational age at birth are risk factors.
A higher propensity for T1DM is inherited:
- T1DM is more than 50% in monozygous twins with long-term follow-up.
- Among first-degree relatives, siblings are more at risk than offspring (5–10% risk by age 20).
- Children of diabetic fathers are at a higher risk (12% vs. 6%) than children of diabetic mothers.

Prevention 

Although there aren't any widely used screening programs right now, healthcare professionals should think about recommending relatives of people with type 1 diabetes for risk evaluation in a clinical research project.

Accompanying Conditions 
Autoimmune conditions include Graves disease, Hashimoto hypothyroidism, myasthenia gravis, pernicious anemia, autoimmune hepatitis, primary adrenal insufficiency (Addison disease), celiac disease, and autoimmune hepatitis.

Introducing History 
newly developed polydipsia and polyuria

In a child who was previously continent, polyuria may manifest as nocturia, bedwetting, or incontinence.
It could be difficult to understand polyuria in youngsters wearing diapers.
When blood glucose levels increase by more than 180 mg/dL (10 mmol/L), polyuria develops.

clinical assessment 

 Loss of weight, increased tiredness, sluggishness, and cramping
DKA and ketosis cause nausea and stomach pain.
Modifications to vision, such as blurriness


Type 2 diabetes and monogenic diabetes are differentially diagnosed when: - Diabetes diagnosed before the age of 6 months should undergo rapid genetic testing.
- A nonobese diabetic infant with no autoantibodies - A strong family history of diabetes without the typical symptoms of type 2 diabetes
Hereditary hemochromatosis, chronic pancreatitis, and secondary diabetes - pancreatic disease
- Endocrine-associated diabetes: neuroendocrine tumors, pheochromocytoma, glucagonoma, Cushing syndrome, and acromegaly
Acute poisonings (salicylate poisoning can mimic DKA) - Drug- or chemical-induced diabetes: glucocorticoids, HIV protease inhibitors, atypical antipsychotics, tacrolimus, cyclosporine, immune checkpoint inhibitors

Laboratory results Initial exams (lab, imaging) Diagnosis criteria for diabetes:
- Random glucose of 200 mg/dL (11.1 mmol/L) in a patient with characteristic hyperglycemia symptoms. - Fasting (>8 hours) glucose 126 mg/dL (7.0 mmol/L) on more than one occasion.
- Oral glucose tolerance test (OGTT): plasma glucose 200 mg/dL 2 hours following a 1.75 g/kg (maximal dosage 75 g) glucose load
HbA1c level of 6.5%
Additional tests to think about:
- Urinalysis for albuminuria (urine albumin:creatinine ratio), hyperglycemia, and ketones
- Islet cell, IAA, GAD, IA2A, and ZnT8A are pancreatic autoantibodies.
urine ketones and serum -hydroxybutyrate (BHB)
- Fructosamine
C-peptide level, if necessary, to distinguish type 2 diabetes, as low or absent C-peptide suggests insulinopenia.
Tests in the Future & Special Considerations
At the time of diagnosis and on a regular basis afterward, patients should be checked for thyroid illness.

Interpretation of Tests

Repeat testing should be done to verify the results if there isn't clear evidence of hyperglycemia.

Management 

With education regarding mealtime insulin dose matching to carbohydrate intake, premeal blood glucose level, and predicted activity, insulin is the cornerstone of therapy.

Goal for premeal blood sugar is between 90 to 130 mg/dL (5.0 and 7.2 mmol/L).
Goal for blood sugar levels before bedtime and during the night is 90 to 150 mg/dL (5.0 to 8.3 mmol/L).
A1c target for children is 7.5% (A1c 7.0% is tolerable if attained without significant hypoglycemia).
A less strict A1c goal (such as 8%) may be appropriate for elderly patients and other particular populations. Adult A1c aim: 7.0% (A1c 6.5% reasonable in select persons).

Medication Multiple daily injections (MDIs) of basal and prandial insulin, or continuous subcutaneous insulin infusion (CSII), are the most common forms of treatment.
Utilize rapid-acting insulin analogs to lower the risk of hypoglycemia.
Different kinds of injectable insulin
- Insulin glargine, insulin detemir, and insulin degludec are long-acting insulin analogs. These shouldn't be mixed in the same syringe as other insulins.
It is possible to combine intermediate-acting insulin (NPH) with other insulins.
- Regular (short-acting) insulin
- Insulin glulisine, insulin aspart, and insulin lispro are examples of rapid-acting insulin analogs.

Initial Line

The gold standard is flexible intensive insulin therapy; MDI or CSII are equally effective.
For patients who are insulin-naive, the total first dose ranges from 0.2 to 0.4 units/kg/day (up to 1.0 unit/kg/day throughout puberty).
50% of the total dose is administered as basal insulin and the remaining 50% as bolus insulin.
MDI protocol:
Prandial, short-acting insulin based on the number of portions of carbs (for example, 1:10, meaning 1 U of insulin for every 10 g of carbohydrates) Basal, long-acting insulin given once or twice a day
- Corrective short-acting insulin for use during meals that is based on premeal blood glucose levels and a sensitivity factor (e.g., 1 U for every 50 mg/dL over 150 mg/dL, where 50 mg/dL is the sensitivity factor).

When there is active patient/family participation, CSII and continuous glucose monitoring (CGM) should be promoted (1).
Next Line
NPH injections twice daily in addition to conventional or rapid-acting insulin (not physiologic, but less expensive and requires fewer injections)
Pramlintide: Postpones stomach emptying, reduces glucagon release from the pancreas, and increases satiety
In cases of concurrent kidney transplantation, recurrent DKA, or severe hyperglycemia, pancreatic and islet transplantation have been demonstrated to normalize glucose levels but require lifelong immunosuppression.

Problems to Refer 

Endocrinology referral is advantageous for type 1 diabetes diagnoses, both new and established.

Further Treatments 
Investigational drugs (not yet FDA-approved): metformin, insulin icodec (super-long-acting insulin), GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-1/SGLT-2 inhibitors. Inhaled rapid-acting insulin (may be used for mealtime coverage).


Surgery If a patient with T1DM is not eating before surgery, basal insulin should be continued.

Prandial insulin should be held in the mornings before procedures or surgeries if patients are not eating.

Admissions 

Patients with T1DM who have just received a diagnosis might need to stay in the hospital while starting insulin therapy.

Follow-Up Patients should lower their basal requirements (temporary basal rate if using an insulin pump) or be instructed to consume 15 to 30 g of carbs before engaging in strenuous exercise to reduce hypoglycemia.
Some people might need to use both strategies to lower hypoglycemia episodes.

patient observation
Every routine appointment should include a blood pressure (BP) check, with a target reading of 130/80 mm Hg.
Using a CGM or a home blood glucose meter, monitor your blood sugar levels at home: At least 4 to 6 times per day should be set aside for glucose tests.
A thorough foot examination at least once a year
HbA1c measurements taken quarterly

High-intensity statin medication should be added to lifestyle therapy for individuals of all ages with diabetes and atherosclerotic cardiovascular disease (ASCVD).
Use a moderate-intensity statin in addition to lifestyle changes for individuals with diabetes who are between the ages of 40 and 75 and older without ASCVD.
Annual examinations:
- Initial dilated comprehensive eye exams within five years of diagnosis and then every one to two years - Albuminuria for the earliest indications of potential nephropathy (urine albumin:creatinine ratio) - Monofilament testing with pinprick, temperature, and vibration sensation for detecting peripheral neuropathy 5 years following diagnosis, followed by yearly
Pneumococcal pneumonia with 13-valent pneumococcal conjugate vaccination (PCV13) is advised before age 2 years. - Annual influenza vaccine in patients 6 months of age. A 23-valent pneumococcal polysaccharide vaccine (PPSV23) should also be administered to individuals between the ages of 2 and 64. PPSV23 is advised at age >65, regardless of vaccination history.
- Hepatitis B immunization for adults aged 19 to 59 who have not had the vaccine. For adults with diabetes who have not received the hepatitis B vaccine and are under 60 years old, consider giving them a 3-dose series.

Patient flexibility in eating is made possible by carbohydrate counting utilizing the insulin-to-carbohydrate ratio for all meals and snacks.

It's crucial to inform patients about their diagnosis, carbohydrate counting, and nutritional advice.

Initial remission or a 3 to 6 month "honeymoon phase" with lower insulin requirements and easier management is the prognosis. With careful blood glucose monitoring, better insulin delivery methods, and optimal glycemic control, the prognosis improves.

Complications include chronic foot ulcers and amputations, microvascular disease (retinopathy, nephropathy, and neuropathy), macrovascular disease (coronary and cerebral artery disease), and hypoglycemia (check blood sugar levels before driving).
DKA, excessive weight gain, heightened risk of serious infection, preeclampsia, and premature birth are all potential risks.