- ACRONYMS AND DEFINITIONS
- A1C - Hemoglobin A1C
- ACR - Albumin-to-creatinine ratio
- ADA - American Diabetes Association
- AN - Acanthosis Nigricans
- ASCVD - Atherosclerotic cardiovascular disease
- CHF - Congestive heart failure
- CKD - Chronic kidney disease
- CrCl - Creatinine clearance
- DKA - Diabetic ketoacidosis
- DM - Diabetes mellitus
- FBS - Fasting blood sugar
- HFpEF - Heart failure with preserved ejection fraction
- HFrEF - Heart failure with reduced ejection fraction
- HHNK - Hyperosmolar hyperglycemic nonketotic syndrome
- HLA - Human Leukocyte Antigens
- LADA - Latent Autoimmune Diabetes in Adults
- OGTT - Oral glucose tolerance test
- T1DM - Type one diabetes mellitus
- T2DM - Type two diabetes mellitus
- UACR - Urinary albumin-to-creatinine ratio
- USPSTF - U.S. Preventive Services Task Force
- PHYSIOLOGY
- Type two diabetes (T2DM), also referred to as non-insulin-dependent diabetes or adult-onset diabetes, is the predominant form of diabetes, accounting for 90 - 95% of all diabetes cases. Rising blood sugars stimulate insulin release from pancreatic beta cells. Insulin, in turn, causes muscle, liver, and fat tissue to take up glucose from the bloodstream. In T2DM, two problems occur: (1) beta cells secrete an inadequate amount of insulin, (2) body tissues become resistant to the effects of insulin. [1]
- T2DM differs from T1DM in that type two diabetics still make insulin, whereas type one diabetics do not
- PREVALENCE OF TYPE 2 DIABETES
- Overview
- It's estimated that 6.3% of the world's population has T2DM. In the U.S., 14.7% of the adult population has diabetes, with 90 - 95% of those cases being type two. The table below provides the prevalence of diabetes in the U.S. based on age, sex, and ethnicity.
Percent of U.S. adult population with diabetes | |||
---|---|---|---|
Characteristic | Diagnosed | Undiagnosed | Total |
Total | 11.3% | 3.4% | 14.7% |
Age in years | |||
18 - 44 | 3.0% | 1.9% | 4.8% |
45 - 64 | 14.5% | 4.5% | 18.9% |
≥ 65 | 24.4% | 4.7% | 29.2% |
Sex | |||
Men | 12.6% | 2.8% | 15.4% |
Women | 10.2% | 3.9% | 14.1% |
Race | |||
White | 11.0% | 2.7% | 13.6% |
Hispanic | 11.1% | 4.4% | 15.5% |
Asian | 11.3% | 5.4% | 16.7% |
Black | 12.7% | 4.7% | 17.4% |
- RISK FACTORS
- Family history
- Family history of T2DM is the strongest known risk factor for developing diabetes
- The table below shows the results from a Swedish study that looked at the risk of diabetes based on family history
Relative with T2DM | Incidence ratio✝ |
---|---|
One parent | 2.0 |
Two parents | 5.3 |
One sibling | 2.8 |
Two siblings | 37.0 |
One sibling / One parent | 4.6 |
One sibling / Two parents | 7.1 |
- Ethnicity
- Certain ethnicities have a higher risk of diabetes than others. The table below shows the prevalence of diabetes by race in U.S. adults.
Race | % of adults with diabetes |
---|---|
Non-hispanic white | 11.9% |
Black | 18.4% |
Hispanics | 20.3% |
Asian-Americans | 27% |
- Obesity
- Obesity (BMI ≥ 30 kg/m²) is a major risk factor for T2DM
- Physical inactivity
- Gestational diabetes
- Women with a history of gestational diabetes are up to 7 times more likely to develop T2DM later in life than women without gestational diabetes. [6]
- Metabolic syndrome
- Metabolic syndrome (obesity, triglycerides > 150 mg/dl, HDL < 40 mg) is a risk factor for T2DM
- Prediabetes
- Patients with prediabetes are at risk of progressing to T2DM
5-year risk of developing T2DM based on A1C value | |
---|---|
A1C value | 5-year incidence of T2DM |
5.0 - 5.5% | < 5 - 9% |
5.5 - 6.0% | 9 - 25% |
6.0 - 6.5% | 25 - 50% |
- Polycystic ovary syndrome (PCOS)
- Women with polycystic ovary syndrome have a higher risk of T2DM
- Medications
- Antipsychotics
- Beta blockers
- Corticosteroids
- Inhaled corticosteroids (Flovent®, Advair®, Beclovent®, etc.) [7]
- Sirolimus (Rapamune®)
- Proton pump inhibitors (e.g. Nexium, Prevacid, Prilosec) [41]
- Statins
- Thiazide diuretics
- ACANTHOSIS NIGRICANS (AN)
- Overview
- Acanthosis Nigricans is a skin condition characterized by darkening (hyperpigmentation) and thickening of the skin (acanthosis nigricans on neck). Affected areas include the neck (up to 99%), armpits, elbows, and knees, and certain ethnicities are affected more than others. [8,9]
- Prevalence of AN by race:
- African-American - 26.8%
- Hispanic - 26.1%
- White - 6%
- All other - 17.1% [9]
- Association with diabetes
- AN is mostly a benign hereditary condition, but it has been associated with insulin resistance and an increased risk of T2DM
- In one study, the prevalence of T2DM in patients with AN was as follows:
- White patients: prevalence of diabetes was 2.1 times greater in patients with AN compared to those without
- Other ethnicities: prevalence of diabetes was 1.47 times greater in patients with AN compared to those without [9]
- ADA recommendations
- Screen the following patients for diabetes:
- Adults with AN and obesity
- Children with AN, obesity, and one or more additional risk factors for diabetes (see screening)
- SYMPTOMS OF TYPE 2 DIABETES
- Overview
- T2DM symptoms often progress slowly over several years, and many patients do not recognize them in the early stages. This is in contrast to T1DM, where symptoms intensify rapidly as insulin secretion declines.
- Classic symptoms of diabetes
- Increased urination (polyuria)
- Increased thirst (polydipsia)
- Weight loss
- Increased hunger and visual changes may also be present, but are less frequent
- SCREENING FOR TYPE 2 DIABETES
ADA T2DM Screening Recommendations |
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Adults
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Children
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Patients taking second generation antipsychotics
|
- USPSTF recommendations
- Screen for prediabetes and T2DM in adults aged 35 to 70 years who are overweight or obese
- The current evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in children and adolescents younger than 18 years
- Screening every 3 years may be reasonable [42]
- DIAGNOSIS OF TYPE 2 DIABETES AND PREDIABETES
- Blood sugar values
- Blood sugar values can be used to diagnose T2DM and prediabetes using one of the three methods below
- Fasting blood sugar
- A fasting blood sugar is defined as no caloric intake for 8 hours prior to testing
- Diabetes: ≥ 126 mg/dl
- Prediabetes: 100 - 125 mg/dl
- Two-hour oral glucose tolerance test (2-hour OGTT)
- During a 2-hour OGTT, the patient consumes a 75 gram load of glucose solution and a blood sugar is drawn 2 hours later
- Diabetes: ≥ 200 mg/dl
- Prediabetes: 140 - 199 mg/dl
- Random blood sugar
- A random blood sugar (drawn without regard to last calorie intake) of ≥ 200 mg/dl when classic symptoms of diabetes are present (e.g. weight loss, polyuria, polydipsia) is diagnostic for diabetes. Random blood sugars are not used to diagnose prediabetes. [1]
- Hemoglobin A1C test
- The hemoglobin A1C test can be used to diagnose T2DM and prediabetes; however, it is less sensitive than a fasting glucose level, as one-third of patients with an A1C < 6.5% will have a fasting glucose ≥ 126. The lower sensitivity appears to be more of an issue in adolescents than adults (see hemoglobin A1C for more). [1,20]
- Diabetes: A1C ≥ 6.5%
- Prediabetes: A1C 5.7 - 6.4%
- PREDIABETES
- Overview
- Prediabetes is a condition where blood sugars run higher than normal but not high enough to reach the criteria for diabetes (see diagnosis). Prediabetes is also referred to as "glucose intolerance," "impaired glucose tolerance," and "impaired fasting glucose."
- The table below shows the 5-year risk of prediabetes progressing to diabetes
5-year risk of developing T2DM based on A1C value | |
---|---|
A1C value | 5-year incidence of T2DM |
5.0 - 5.5% | < 5 - 9% |
5.5 - 6.0% | 9 - 25% |
6.0 - 6.5% | 25 - 50% |
- Studies
- The studies below evaluated the efficacy of medications and lifestyle changes (exercise, diet) in preventing T2DM in prediabetics
- The Diabetes Prevention Program trial enrolled 3234 patients with prediabetes
Main inclusion criteria
- Age ≥ 25 years
- BMI ≥ 24 (≥ 22 in Asians)
- Fasting blood glucose of 95 - 125 mg/dl
- OGTT of 140 - 199 mg/dl
Main exclusion criteria
- Taking a medication that affects blood glucose
Baseline characteristics
- Average age 50.6 years
- Average BMI - 34
- Average weight - 207 lbs (94 kg)
- Average fasting glucose 106.5 mg/dl
- Average HgA1C - 5.91%
Randomized treatment groups
- Group 1 (1082 patients) - Placebo twice a day
- Group 2 (1073 patients) - Metformin 850 mg twice a day
- Group 3 (1079 patients) - Intensive lifestyle intervention (7% weight loss + 150 minutes exercise/week)
- Groups 1 and 2 were given standard lifestyle recommendations in written form
- Group 3 was given one-on-one counseling during the first 24 weeks
Primary outcome: Diagnosis of diabetes based on an annual 2-hour OGTT ≥ 200 mg/dl or semiannual fasting glucose ≥ 126 mg/dl
Results
Duration: Average of 2.8 years | ||||
Outcome | Placebo | Metformin | Diet/Exercise | Comparisons |
---|---|---|---|---|
Primary outcome (%/year) | 11% | 7.8% | 4.8% | p<0.001 for all comparisons |
Weight loss | 0.22 lbs | 4.6 lbs | 12.3 lbs | p<0.001 for all comparisons |
Gastrointestinal symptoms | 30.7% | 77.8% | 12.9% | p<0.05 for all comparisons |
|
Findings: Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
- The ACT NOW study enrolled 602 patients with impaired glucose tolerance
Main inclusion criteria
- OGTT of 140 - 199 mg/dl
- BMI ≥ 25
- At least one risk factor for diabetes
Main exclusion criteria
- Treatment with diabetes medications within 1 year
- Cardiovascular disease
- Serum creatinine ≥ 1.6 mg/dl in men or ≥ 1.5 mg/dl in women
- Significant liver disease
Baseline characteristics
- Average age 52 years
- Average BMI - 34
- Average HgA1C - 5.5%
- Average fasting blood sugar - 105 mg/dl
- Average 2-hour OGTT - 168 mg/dl
Randomized treatment groups
- Group 1 (303 patients) - Pioglitazone 45 mg once daily
- Group 2 (299 patients) - Placebo once daily
- Pioglitazone was started at 30 mg once daily and increased to 45 mg after 1 month
- Patients were followed-up at 2, 4, 6, 8, 10, and 12 months and every 3 months thereafter
- Fasting blood sugar was measured at every visit and 2-hour OGTT was performed annually
Primary outcome: Development of diabetes defined as fasting blood sugar ≥ 126 mg/dl or 2-hour OGTT ≥ 200 mg/dl
Results
Duration: Median of 2.4 years | |||
Outcome | Pioglitazone | Placebo | Comparisons |
---|---|---|---|
Primary outcome | 5% | 16.7% | p<0.001 |
Incidence of worsening edema | 12.9% | 6.4% | p=0.007 |
Weight gain | 8.36 lbs | 1.32 lbs | p<0.001 |
Dropout rate | 29.7% | 23.7% | N/A |
Findings: As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema
- The XENDOS trial enrolled 3305 patients with a BMI ≥ 30 and an average body weight of 242 pounds
Main inclusion criteria
- 30 - 60 years of age
- BMI ≥ 30
- Normal blood sugar or impaired glucose tolerance (FBS of < 120 mg/dl and OGTT of 120 - 180 mg/dl)
Main exclusion criteria
- Diabetes
- Cardiovascular disease
- Gastrointestinal disease
Baseline characteristics
- Average age 43 years
- Average weight - 242 pounds (110 kg)
- Average BMI - 37
- Average fasting blood sugar - 83 mg/dl
- Patients with impaired glucose tolerance - 21%
Randomized treatment groups
- Group 1 (1640 patients) - Orlistat 120 mg three times a day + weight loss counseling
- Group 2 (1637 patients) - Placebo + weight loss counseling
- All patients were prescribed a diet with a caloric deficit of 800 calories a day
- 2-hour OGTT was performed every 6 months
Primary outcome: Time to onset of type 2 diabetes and change in body weight after 4 years
Results
Duration: 4 years | |||
Outcome | Orlistat | Placebo | Comparisons |
---|---|---|---|
Primary outcome (diabetes) | 6.2% | 9% | HR 0.63, 95% CI [0.46 - 0.86], p=0.0032 |
Primary outcome (weight loss) | 12.8 lbs | 6.6 lbs | p<0.001 |
Dropouts | 48% | 66% | p<0.0001 |
LDL cholesterol (% decrease from baseline) | 12.8% | 5.1% | p<0.01 |
GI side effects (during year 1) | 91% | 65% | N/A |
GI side effects (during year 4) | 36% | 23% | N/A |
|
Findings: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the impaired glucose tolerance subgroup; weight loss was similar in subjects with impaired glucose tolerance or normal glucose tolerance.
- The STOP-NIDDM trial enrolled 1429 prediabetics
Main inclusion criteria
- Age 40 - 70 years
- BMI 25 - 40
- OGTT of 140 - 200 mg/dl and FBS of 100 - 139 mg/dl
Baseline characteristics
- Average age 54 years
- Average weight - 191 lbs (87 kg)
- Average BMI - 31
- Average fasting glucose - 112 mg/dl
- Average 2-hour GTT - 167 mg/dl
Randomized treatment groups
- Group 1 (682 patients) - Acarbose with a target dose of 100 mg three times a day (mean dose achieved 194 mg/day)
- Group 2 (686 patients) - Placebo three times a day
- All patients were counseled on weight loss and encouraged to exercise
Primary outcome: Development of diabetes based on a 2-hour OGTT of > 200 mg/dl
Results
Duration: Average of 3.3 years | |||
Outcome | Acarbose | Placebo | Comparisons |
---|---|---|---|
Primary outcome (percent with diabetes) | 32% | 42% | HR 0.75, 95%CI [0.63 - 0.90], p=0.0015 |
Flatulence | 68% | 27% | N/A |
Diarrhea | 32% | 17% | N/A |
Abdominal pain | 17% | 12% | N/A |
Dropout rate | 31% | 19% | N/A |
|
Findings: Acarbose could be used, either as an alternative or in addition to changes in lifestyle, to delay development of type 2 diabetes in patients with impaired glucose tolerance
- The NAVIGATOR study enrolled 9306 patients with impaired glucose tolerance and either cardiovascular disease or risk factors for cardiovascular disease
Main inclusion criteria
- Age ≥ 50 years
- Fasting glucose of 95 - 126 mg/dl
- Documented CVD or risk factors for CVD
Main exclusion criteria
- Significant liver disease
- Serum creatinine > 2.5 mg/dl
- Current use of ACE inhibitor or ARB
- Use or oral DM med or insulin within past 5 years
- NYHA class III or IV heart failure
Baseline characteristics
- Average age 64 years
- Average BMI - 30.5
- Average BP - 140/83
- History of cardiovascular disease - 24%
- Average HgA1C - 5.8%
- Average fasting glucose - 110 mg/dl
Randomized treatment groups
- Group 1 (4645 patients) - Nateglinide 60 mg three times a day before meals
- Group 2 (4661 patients) - Placebo three times a day
- Nateglinide was started at 30 mg before meals and increased to 60 mg after 2 weeks
- Fasting blood sugar was measured every 6 months for 3 years, then annually. Oral glucose tolerance tests were also performed annually.
- All participants were required to participate in a lifestyle modification program
- Another factor in the trial randomized patients to valsartan
Primary outcomes:
- 1. Progression to diabetes
- 2. Composite of death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina
Results
Duration: Progression to diabetes - median of 5 years | Composite cardiovascular outcome - median of 6.3 years | |||
Outcome | Nateglinide | Placebo | Comparisons |
---|---|---|---|
Primary outcome (diabetes incidence) | 36% | 33.9% | HR 1.07 95%CI [1.0 - 1.15], p=0.05 |
Primary outcome (cardiovascular outcomes) | 14.2% | 15.2% | HR 0.93 95%CI [0.83 - 1.03], p=0.16 |
Myocardial infarction | 2.9% | 3.1% | HR 0.95 95%CI [0.75 - 1.20], p=0.66 |
Overall mortality | 6.7% | 6.7% | HR 1.0 95%CI [0.85 - 1.17], p=0.98 |
Hypoglycemia incidence | 19.6% | 11.3% | p<0.001 |
Drug discontinuation at 5 years | 30.1% | 29% | N/A |
Findings: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes.
- A study in the NEJM enrolled 522 patients with impaired glucose tolerance
Main inclusion criteria
- Age 40 - 65 years
- OGTT of 140 - 200 mg/dl
- BMI ≥ 25
Main exclusion criteria
- Fasting blood glucose ≥ 140 mg/dl
- Diagnosis of diabetes
Baseline characteristics
- Average age 55 years
- Average BMI - 31
- Average fasting blood sugar - 109 mg/dl
- Average 2-hour OGTT - 159 mg/dl
Randomized treatment groups
- Group 1 (265 patients) - Detailed advice on diet and exercise that included ongoing meetings with a nutritionist and voluntary weight training groups (intervention group)
- Group 2 (257 patients) - Oral and written information on diet and exercise, but no individual therapy (control group)
- All subjects underwent annual 2-hour OGTT
Primary outcome: Development of diabetes defined as fasting blood sugar ≥ 140 mg/dl or 2-hour OGTT ≥ 200 mg/dl
Results
Duration: Average of 3.2 years | |||
Outcome | Intervention | Control | Comparisons |
---|---|---|---|
Primary outcome (diabetes incidence at 4 years) | 11% | 23% | HR 0.40 95%CI [0.3 - 0.7], p<0.001 |
Percent of body weight lost at 1 year | 4.7% | 0.9% | p<0.001 |
Weight loss at 2 years | 7.7 lbs | 1.76 lbs | p<0.001 |
Dropouts | 8.7% | 6.6% | N/A |
Findings: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects
- ADA recommendations for prediabetes
- Monitor for development of T2DM at least annually
- Refer adults with overweight/obesity at high risk of T2DM, as typified by the Diabetes Prevention Program (DPP), to an intensive lifestyle behavior change program consistent with the DPP to achieve and maintain 7% loss of initial body weight, and increase moderate-intensity physical activity (such as brisk walking) to at least 150 min/week.
- Metformin therapy for prevention of type 2 diabetes should be considered in adults with prediabetes, as typified by the DPP, especially those aged 25–59 years with BMI ≥ 35, higher fasting plasma glucose (≥ 110 mg/dL), and higher A1C (≥ 6.0%), and in women with prior gestational diabetes mellitus
- Long-term use of metformin may be associated with biochemical vitamin B12 deficiency; consider periodic measurement of vitamin B12 levels in metformin-treated patients, especially in those with anemia or peripheral neuropathy. [44]
- Summary
- Weight loss and exercise are superior to medications in preventing diabetes. Medications most likely treat early diabetes and mask its diagnosis as opposed to truly preventing it.
- Overweight patients with prediabetes and mild diabetes should pursue weight loss and exercise measures aggressively, with the understanding that they have control over their condition. Metformin may be considered in patients who do not respond to these measures.
- WEIGHT LOSS FOR T2DM
- Overview
- Weight loss can have a profound effect on blood sugars in overweight type two diabetics, even leading to remission in many cases. The DIRECT study detailed below demonstrated just how effective weight loss is for T2DM.
- A study in the Lancet enrolled 306 overweight patients with T2DM
Main inclusion criteria
- Age 20 - 65 years
- Diagnosed with T2DM within the previous 6 years
- BMI 27 - 45
Main exclusion criteria
- Current insulin use
- A1C ≥ 12%
- CrCl < 30 ml/min
- Weight loss > 5 kg within the past 6 months
Baseline characteristics
- Average age - 53 years
- Average BMI - 35
- Average weight - 220 lbs (100 kg)
- Average A1C - 7.6% (SD 1.12%)
- Average time since diagnosis - 3 years
- Number of oral DM meds: 0 - 24% | 1 - 48% | ≥ 2 - 27%
Randomized treatment groups
- Group 1 (149 patients) - Weight loss program (intervention group)
- Group 2 (149 patients) - Usual care
- In Group 1, all DM medications were discontinued on Day 1 of the weight loss program. In Group 2, DM meds were continued.
- Weight loss program consisted of 3 months (extendable up to 5 months if wished by participant) of a total diet replacement phase using a low energy formula diet (825–853 kcal/day; 59% carbohydrate, 13% fat, 26% protein, 2% fiber). After that, structured food reintroduction of 2 – 8 weeks (about 50% carbohydrate, 35% total fat, and 15% protein), and an ongoing structured program with monthly visits for long-term weight loss maintenance.
- In both groups, subjects were encouraged to continue their usual amount of physical activity
- The study was a cluster randomized trial at 49 primary care practices
Primary outcome: The co-primary outcomes were a reduction in weight of 33 lbs (15 kg) or more, and remission of diabetes, defined as HbA1c
less than 6.5% after at least 2 months off all antidiabetic medications, from baseline to month 12
Results
Duration: 12 months | |||
Outcome | Intervention | Usual care | Comparisons |
---|---|---|---|
Primary outcome (weight loss ≥ 33 lbs) | 24% | 0% | p<0.0001 |
Primary outcome (remission of diabetes) | 46% | 4% | p<0.0001 |
Average weight loss | 22 lbs | 2.2 lbs | p<0.0001 |
Average change in A1C | -0.9% | +0.1% | p<0.0001 |
Using DM meds | 26% | 82% | N/A |
|
Remission of diabetes in all patients by weight loss | ||||
---|---|---|---|---|
Weight gain | 0 - 11 lbs | 11 - 22 lbs | 22 - 33 lbs | ≥ 33 lbs |
0% | 7% | 34% | 57% | 86% |
Findings: Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care
- A follow-up study looked at 2-year outcomes among participants in the DIRECT study
Results
Duration: 2 years | |||
Outcome | Intervention | Usual care | Comparisons |
---|---|---|---|
Weight loss ≥ 33 lbs | 11% | 2% | p=0.0023 |
Remission of diabetes | 36% | 3% | p<0.0001 |
Average weight loss | 16.7 lbs | 5 lbs | p<0.01 |
Average change in A1C | -0.5% | 0% | p<0.01 |
Using DM meds | 40% | 84% | N/A |
Remission of diabetes in all patients by weight loss at 2 years | |||
---|---|---|---|
< 11 lbs | 11 - 22 lbs | 22 - 33 lbs | ≥ 33 lbs |
5.2% | 29% | 60% | 70% |
Findings: The DIRECT program sustained remissions at 24 months for more than a third of people with type 2 diabetes. Sustained remission was linked to the extent of sustained weight loss.
- Summary
- In the DIRECT study, 60% of overweight diabetics who lost 22 - 33 pounds had disease remission at two years. Overweight diabetics with any severity of diabetes are likely to see a significant benefit from weight loss. See weight loss review for more.
- BLOOD SUGAR GOALS
- See blood sugar goals in diabetes for recommendations on target blood sugar values and A1C values
- TREATMENT RECOMMENDATIONS FOR TYPE 2 DIABETES
ADA T2DM Treatment Recommendations for Adults |
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Overview
|
Treatment recommendations are based on the following comorbidities and/or goals:
|
Patients with ASCVD or indicators of high risk - patients with established CVD (e.g. CAD, stroke, PAD) and those at high risk, defined as ≥ 55 years with two or more additional risk factors (obesity, hypertension, smoking, dyslipidemia, albuminuria)s
|
Patients with heart failure (HFrEF and HFpEF)
|
Patients with chronic kidney disease - GFR < 60 ml/min or albuminuria (ACR ≥ 30 mg/g)
|
Weight loss is the primary goal
|
Glycemic management is the primary goal
|
Studies
|
ADA T2DM Treatment Recommendations for Youth (10 - 19 years) |
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Step 1 - initial therapy
|
Step 2 - order pancreatic autoantibodies (see T1DM autoimmune antibodies)
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- EARLY INSULIN THERAPY IN TYPE 2 DIABETES
- Overview
- A handful of small studies have shown that treating newly-diagnosed type two diabetics with intensive insulin therapy can cause beta cells to recover function and maintain normal glucose levels off meds. One of the larger studies to look at this effect is detailed below.
- A study in the Lancet enrolled 382 patients with newly diagnosed type 2 diabetes
Main inclusion criteria
- Newly diagnosed type 2 diabetes
- No previous diabetes therapy
Main exclusion criteria
- Diabetic complications
- Positive for GAD65A antibodies (islet cell autoantibody)
- Maturity onset diabetes in youth and mitochondrial diabetes mellitus
Baseline characteristics
- Average age 51 years
- Average BMI - 25
- Average fasting blood sugar - 207 mg/dl
- Average HgA1C - 9.7%
Randomized treatment groups
- Group 1 (137 patients) - Patients were put on an insulin pump
- Group 2 (124 patients) - Patients were put on intensive insulin therapy with multiple insulin injections a day
- Group 3 (121 patients) - Patients were treated with sulfonylurea and metformin
- After patients maintained normal blood sugars for 2 weeks, all medications were stopped and patients were continued on diet and exercise therapy alone for one year
- Patients who did not achieve normal blood sugars within 2 weeks were excluded from the study
- Patients were followed-up monthly during the first 3 months, then every 3 months
Primary outcome: Relapse back into elevated blood sugars at 1 year. Relapse was defined as fasting blood sugar > 126 mg/dl or 2-hour postprandial
glucose > 180 mg/dl.
Results
Duration: 12 months | ||||
Outcome | Insulin pump | Intensive insulin | Oral meds | Comparisons |
---|---|---|---|---|
Primary outcome (relapse at 1 year) | 49% | 55% | 73% | 1 and 2 vs 3 p=0.0012 |
Achieved normal blood sugar | 97% | 95% | 84% | N/A |
Average time to normal blood sugar | 4 days | 5.6 days | 9.3 days | N/A |
Hypoglycemia during intensive phase | 31% | 28% | 19% | N/A |
|
Findings: Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes has favourable outcomes on recovery and maintenance of beta-cell function and protracted glycaemic remission compared with treatment with oral hypoglycemic agents
- Summary
- Early intensive insulin therapy appears to renew beta cell function in some type two diabetics. However, this approach is complex and impractical given the number of T2DM therapies that are now available.
- A similar study in youth with newly-diagnosed T1DM did not find a beneficial effect of intensive insulin therapy on beta cell function. [PMID 36826834]
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