Depression & Insulin Sensitivity in Adolescents

There has been rapid escalation of type 2 diabetes (T2D) rates in adolescents. Early-onset
T2D (<20y) typically shows a more aggressive course than adult-onset T2D and
disproportionately affects girls from disadvantaged, racial/ethnic groups. This group of
girls also is at heightened risk for depression, and depression and T2D are linked.
Depressive symptoms often manifest in adolescence and are a prospective risk factor for
worsening of insulin sensitivity, the major physiological precursor—in combination with
deterioration of pancreatic β-cell capacity to secrete insulin—in the path to T2D. The
effects of depression on poor insulin sensitivity remain even after accounting for adiposity.
In theory, depressive symptoms may worsen insulin sensitivity through stress-induced
behaviors (e.g., disinhibited eating, physical inactivity, sleep disturbance) and
stress-induced physiological causal mechanisms (e.g., hypercortisolism). The central theme of
this study is that intervening to reduce depressive symptoms in adolescents at-risk for T2D
may offer an innovative, targeted approach to ameliorate insulin resistance and to,
consequently, preserve β-cell function and lessen T2D risk. In preliminary data, the
investigators found initial evidence that a 6-week cognitive-behavioral group decreased
depressive symptoms and prevented worsening of insulin sensitivity 1 year later in overweight
and obese girls with moderate depressive symptoms and a family history of T2D, in comparison
to a 6-week health education control group. Directly extending these findings, the primary
aims of this study are: 1) to assess the efficacy of a 6-week cognitive-behavioral depression
group vs. a 6-week health education control group for improving insulin sensitivity and
preserving β-cell function in racially/ethnically diverse adolescent girls at-risk for T2D
with moderate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating,
physical activity, and sleep as behavioral explanatory mediators underlying the relationship
between decreases in depressive symptoms and improvements in insulin sensitivity and β-cell
function over 1 year and 3) to test changes in cortisol awakening response, diurnal cortisol
rhythm, and total daily cortisol output as physiological mechanisms explaining the
relationship between decreases in depressive symptoms and improvements in insulin sensitivity
and β-cell function over 1 year.

Inclusion Criteria:

- Female

- Age 12-17 years

- Body mass index (BMI) ≥85th percentile for age & sex

- Center for Epidemiologic Studies-Depression Scale (CES-D) >20

- English speaking

- ≥1 first- or second-degree family member with type 2 diabetes (T2D), prediabetes, or
gestational diabetes

- Good general health

Exclusion Criteria:

- Pregnancy or breastfeeding

- Type 2 diabetes as indicated by fasting glucose≥126 mg/dL or 2-hour glucose>200 mg/dL
or Hba1c>=6.5

- Medication affecting mood, weight, cortisol, or insulin sensitivity, including insulin
sensitizers (e.g., metformin), anti-depressants, and stimulants

- Major psychiatric disorder that, in the opinion of the investigators, would impede
study compliance and necessitate more intensive treatment, including major depressive
disorder, bipolar disorder, posttraumatic stress disorder, panic disorder,
obsessive-compulsive disorder, schizophrenia, conduct disorder, alcohol and substance
abuse, and anorexia/bulimia nervosa

- Psychotherapy or structured weight loss program

- Active suicidal ideation or suicidal behavior